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Gao Y, Rong L, Cui J, Cheng W, Fu L, Fan G, Wang H, Yu J, Li Z, Liu D, Zhao S, Chen H, Qin J, Tao M, Jin Z, Chen Y, Li Y. Artificial lipids and macrophage membranes coassembled biomimetic nanovesicles for thoracic aortic dissection treatment. J Control Release 2025; 383:113844. [PMID: 40379216 DOI: 10.1016/j.jconrel.2025.113844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/29/2025] [Accepted: 05/12/2025] [Indexed: 05/19/2025]
Abstract
Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease characterized by rapid progression and high morbidity. Current efforts to develop effective treatment strategies focus on targeting apoptotic aortic endothelial cells and mitigating inflammation. Here, inspired by the inflammation-neutralizing capacity of functional cells, we present multifunctional biomimetic nanovesicles (MM-LPs) co-assembled from macrophage membranes and synthetic lipids for the targeted delivery of Senkyunolide I (SEI) in TAD treatment. The integration of macrophage membranes endows MM-LPs with the ability to selectively target activated vascular endothelial cells (VECs) while adsorbing proinflammatory cytokines to suppress inflammation. Additionally, these nanoparticles enable the controlled release of SEI, leading to significant anti-apoptotic effects. Leveraging these advantages, MM-LPs effectively mitigated VECs activation, reduced apoptosis, and prevented disease progression and rupture in a BAPN (β-aminopropionitrile monofumarate)-induced mouse model of TAD. Furthermore, this system significantly reduced SEI-associated toxicity and adverse effects on the liver and kidneys. These findings highlight the potential of combining natural macrophage membranes with synthetic lipids to develop a multifunctional biomimetic drug delivery system for treating VECs dysfunction while minimizing drug-related side effects.
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Affiliation(s)
- Yanlin Gao
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Li Rong
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Jing Cui
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China; Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Wei Cheng
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Lin Fu
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, China
| | - Guangpu Fan
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Haiyan Wang
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Jiaqi Yu
- Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Zhen Li
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Dinghong Liu
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Sheng Zhao
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Houliang Chen
- Department of Cardiology, Hefei Third Clinical College, Anhui Medical University (Hefei Third People's Hospital), Hefei 230041, Anhui, China
| | - Junchao Qin
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Miaomiao Tao
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China
| | - Zhechuan Jin
- Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Yu Chen
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China.
| | - Yuyu Li
- Cardiac and Vascular Center, Anhui No.2 Provincial People's Hospital, Hefei 230041, Anhui Province, China; Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
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Xin Y, Lyu S, Wang J, Wang Y, Shu Y, Liang H, Yang Y. Predictive value of inflammatory indexes in in-hospital mortality for patients with acute aortic dissection. BMC Cardiovasc Disord 2025; 25:323. [PMID: 40281397 PMCID: PMC12023605 DOI: 10.1186/s12872-025-04775-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND The purpose of this study was to assess the relationship between admission inflammatory indexes neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), and the risk of in-hospital all-cause mortality in acute aortic dissection (AAD) patients. METHODS A retrospective analysis was conducted on 597 AAD patients (Stanford classification: Stanford type A 365 patients, Stanford type B 232 patients) at a single center. Outcomes were the incidence of in-hospital all-cause mortality. The risk of all-cause death was compared between the groups with low and high inflammatory indexes using the Kaplan-Meier curve. The association between admission inflammatory indexes and outcomes was evaluated using the Cox regression model and restricted cubic splines (RCS). Stratified analysis was performed based on AAD type, age (< 50 years or ≥ 50 years), and gender. RESULTS The Kaplan-Meier curves revealed statistically significant differences in outcomes among the low and high inflammatory indexes groups. Cox regression analysis revealed that the in-hospital mortality risk was significantly high in the high inflammatory index groups. MLR was the strongest associated with in-hospital mortality risk. The RCS curve revealed that NLR was non-linearly and J-shaped correlated with in-hospital mortality, and MLR and SII were linearly correlated with in-hospital mortality. Stratified analysis showed interactions between NLR, MLR, and SII and AAD type and age for the risk of in-hospital mortality. CONCLUSION Admission high inflammatory indexes were independently associated with an increased risk of in-hospital all-cause mortality in AAD patients. The inflammatory indexes NLR, MLR, and SII may be useful indicators for predicting in-hospital all-cause mortality in AAD patients.
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Affiliation(s)
- Yijing Xin
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Siqi Lyu
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Jingyang Wang
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yimeng Wang
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yuyuan Shu
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Hanyang Liang
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yanmin Yang
- Emergency Center, State Key Laboratory of Cardiovascular Disease of China, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
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Suolang Y, Gao Y, Sun C, Zhang S. Predictive Value of the White Blood Cells Count for the Prognosis of Hospitalized Patients with Acute Aortic Dissection. Rev Cardiovasc Med 2025; 26:26347. [PMID: 40351700 PMCID: PMC12059737 DOI: 10.31083/rcm26347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/09/2024] [Accepted: 12/09/2024] [Indexed: 05/14/2025] Open
Abstract
Objective Our study evaluated the prognostic significance of white blood cells (WBC) count and WBC subsets in relation to the risk of mortality in acute aortic dissection (AAD) patients during their hospital stay. Methods We included 833 patients with AAD in this retrospective study. The primary outcome was in-hospital mortality. Cox regression analysis was employed to determine the independent risk factors for mortality in patients with AAD. Amidst the low- and high-WBC groups, we use Kaplan‒Meier survival analysis to compare the cumulative survival rates of patients with AAD. Results Within 342 patients with type A AAD, patients belonging to the high-WBC group exhibited a notably higher mortality rate compared to patients in the low-WBC group. Kaplan-Meier analysis exhibited that the patients in high-WBC patients had a significantly higher mortality rate. Multivariable Cox regression analysis demonstrated that an elevated WBC was an independent impact factor of in-hospital mortality of patients with type A AAD (hazard ratio, 2.01; 95% confidence interval (CI): 1.24 to 3.27; p = 0.005). Corresponding outcomes were witnessed in 491 patients with type B AAD. Conclusions An elevated WBC count was strongly correlated with an elevated risk of mortality in hospitalized patients afflicted with either type A or type B AAD.
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Affiliation(s)
- Yuzhen Suolang
- Department of Emergency Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
- Disaster Medical Center, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Yizhu Gao
- Department of Emergency Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
- Disaster Medical Center, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Changli Sun
- Chengdu Shang Jin Nan Fu Hospital/Shang Jin Hospital of West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Shu Zhang
- Department of Emergency Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
- Disaster Medical Center, Sichuan University, 610041 Chengdu, Sichuan, China
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Zhang Z, Wang H, Kan X, Zhang X, Xu S, Cai J, Guo J. The interplay of ferroptosis and oxidative stress in the pathogenesis of aortic dissection. Front Pharmacol 2025; 16:1519273. [PMID: 39974735 PMCID: PMC11835687 DOI: 10.3389/fphar.2025.1519273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 01/09/2025] [Indexed: 02/21/2025] Open
Abstract
Aortic dissection (AD) is a life-threatening vascular condition marked by the separation or tearing of the aortic media. Ferroptosis, a form of iron-dependent programmed cell death, occurs alongside lipid peroxidation and the accumulation of reactive oxygen species (ROS). The relationship between ferroptosis and AD lies in its damaging effect on vascular cells. In AD, ferroptosis worsens the damage to vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), thereby weakening the vascular wall's structural integrity and accelerating the onset and progression of the condition. However, the molecular mechanisms through which ferroptosis regulates the onset and progression of AD remain poorly understood. This article explores the relationship between ferroptosis and AD.
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Affiliation(s)
- Zhaoshan Zhang
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Haichao Wang
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Xi Kan
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Xiaozhao Zhang
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Senping Xu
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Jie Cai
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
| | - Jiawei Guo
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, China
- Department of Stomatology, The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, China
- Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou, China
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Zhuang X, Zarif M, Shen Y, Zhang Z, He J, Xie L, Wu Q, Lin X, Chen K, Tian Y, Lin Y, Zhang Y, Cai Z, Qiu Z, Chen L. Hepatic Abnormal Secretion of Apolipoprotein C3 Promotes Inflammation in Aortic Dissection. J Am Heart Assoc 2025; 14:e037172. [PMID: 39846283 PMCID: PMC12074741 DOI: 10.1161/jaha.124.037172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 11/22/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Apolipoprotein C3 (apo C3) is primarily secreted by the liver and is involved in promoting sterile inflammation and organ damage under pathological conditions. Previous studies have shown that apo C3 is abundant in the plasma exosomes of patients with aortic dissection (AD), but its specific role in AD remains unclear. METHODS AND RESULTS In vivo, adeno-associated virus was used to knock down hepatic apo C3 expression in an AD mouse model to assess the impact of liver-derived apo C3 on the development of AD. In vitro, recombinant apo C3 protein was added to the culture medium of J774A.1 macrophages to evaluate its effect on macrophage polarization and to identify the underlying mechanisms. Additionally, the effect of apo C3 on the function of aortic endothelial and smooth muscle cells was explored. Apo C3 in the aortas of AD mice was found to originate from abnormal hepatic secretion, which enters the bloodstream and subsequently deposits in the aorta. Adeno-associated virus-mediated hepatic apo C3 knockdown significantly reduced AD incidence (P=0.0036), macrophage infiltration (P=0.0004), and collagen deposition in the aorta (P=0.0016). Similarly, inhibiting the apo C3 receptor Toll-like receptor 2 significantly lowered AD incidence (P=0.0352). In vitro, recombinant apo C3 protein promoted M1 polarization and matrix metalloproteinase secretion in macrophages by activating the Toll-like receptor 2/NLR family pyrin domain containing 3 pathway. Additionally, apo C3 increased adhesion molecule expression in endothelial cells and induced inflammation, chemotaxis, and apoptosis in vascular smooth muscle cells. CONCLUSIONS Our findings highlight the role of abnormally secreted hepatic apo C3 in promoting aortic inflammation.
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Affiliation(s)
- Xinghui Zhuang
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Mohammad Zarif
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Yue Shen
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Zhaofeng Zhang
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Jian He
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Linfeng Xie
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Qingsong Wu
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Xinfan Lin
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Keyuan Chen
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Yue Tian
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Yong Lin
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Yuling Zhang
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
| | - Ziwen Cai
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
- Fujian Provincial Center for Cardiovascular MedicineFuzhouChina
| | - Zhihuang Qiu
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
- Fujian Provincial Center for Cardiovascular MedicineFuzhouChina
| | - Liangwan Chen
- Department of Cardiovascular SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University)Fujian Province UniversityFuzhouChina
- Fujian Provincial Center for Cardiovascular MedicineFuzhouChina
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Diao YF, Chen ZB, Gu JX, Xu XY, Lin WF, Yuan CZ, Xiong JQ, Li MH, Ni BQ, Zhao S, Shao YF, Zhang YY, Liu H. Incorporating Circulating Plasma Interleukin-10 Enhanced Risk Predictability of Mortality in Acute Type A Aortic Dissection Surgery. Rev Cardiovasc Med 2025; 26:26334. [PMID: 40026520 PMCID: PMC11868896 DOI: 10.31083/rcm26334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/13/2024] [Accepted: 10/30/2024] [Indexed: 03/05/2025] Open
Abstract
Background Acute type A aortic dissection (TAAD) is a life-threatening cardiovascular emergency with a high mortality rate. The peri-operative factors influencing in-hospital mortality among surgically treated TAAD patients remain unclear. This study aimed to identify key peri-operative risk factors associated with in-hospital mortality. Methods Peri-operative laboratory data, surgical strategies, and TAAD-related risk factors, associated with mortality, were collected. Machine learning techniques were applied to evaluate the impact of various parameters on in-hospital mortality. Based on the findings, a nomogram model was developed and validated using area under the receiver operating characteristic curve (AUC) analysis, calibration plots, and internal validation methods. Results A total of 199 patients with TAAD were included in the study cohort, which was divided into derivation and validation cohorts. Using the least absolute shrinkage and selection operator (LASSO) regression method, 66 features were narrowed down to six key predictors. These included age, lymphocyte count, use of continuous renal replacement therapy (CRRT), cardiopulmonary bypass (CPB) time, duration of mechanical ventilation, and postoperative interleukin-10 (IL-10) levels, all of which were identified as significant risk factors for in-hospital mortality following TAAD surgery. Conclusions We developed and validated a predictive model, presented as a nomogram, to estimate in-hospital survival in patients with TAAD. Post-operative IL-10 was identified as an independent prognostic factor for patients with TAAD. The combination of IL-10 with five additional indicators significantly improved the predictive accuracy, demonstrating superiority over the use of any single variable alone. Clinical Trial Registration This study protocol was registered at ClinicalTrials.gov (NCT04711889). https://clinicaltrials.gov/study/NCT04711889.
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Affiliation(s)
- Yi-fei Diao
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Zhi-bin Chen
- Department of Cardiovascular Surgery, First Affiliated Hospital of Guangzhou Medical University, 510120 Guangzhou, Guangdong, China
| | - Jia-xi Gu
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Xin-yang Xu
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Wen-feng Lin
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Chun-ze Yuan
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Jia-qi Xiong
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Ming-hui Li
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Bu-qing Ni
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Sheng Zhao
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Yong-feng Shao
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
| | - Ying-yuan Zhang
- Department of Cardiovascular Surgery, First Affiliated Hospital of Guangzhou Medical University, 510120 Guangzhou, Guangdong, China
| | - Hong Liu
- Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, China
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Tsuchida K, Oyanagi N, Tanaka K, Hosaka Y, Takahashi K, Oda H. Determinants of Trunk Muscle Size Decrease in Patients with Type B Acute Aortic Dissection. Int Heart J 2025; 66:106-113. [PMID: 39828333 DOI: 10.1536/ihj.24-483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Trunk muscle decrease is reportedly associated with an increased risk of multiple adverse clinical outcomes. Acute aortic dissection (AAD) involves a systemic inflammatory response which is associated with exaggerated muscle protein catabolism. AAD requires prolonged hospitalization and potentially exacerbates muscle size decrease.Cross-sectional areas (CSA) of both the bilateral psoas muscle area (PMA) and L4 vertebral body were determined using CT scans on admission to calculate the psoas-lumbar vertebral index (PLVI = bilateral PMA/L4 body CSA) in 141 hospitalized type B AAD patients. Serial CT scans within 30 days were performed to investigate PLVI change (%/day) calculated as: (PLVI at follow-up - PLVI at admission) /PLVI at admission × 100/follow-up interval (days). Patients were categorized into a large decrease of PLVI (LD) group and a modest decrease and increase of PLVI (MDI) group according to the median value of decreased PLVI change (-0.48%/day).A large PLVI decrease was correlated with a higher peak C-reactive protein (CRP) value (13.8 versus 10.9 mg/dL, P = 0.010), and larger false lumen (FL) diameter (13.6 versus 11.4 mm, P = 0.015). The days until ambulation and the length of hospital stay were slightly longer in the LD group than in the MDI group (days until ambulation, P = 0.111; length of hospital stay, P = 0.053). Logistic regression model analysis demonstrated a higher peak CRP level (OR = 3.43; 95% CI, 1.50-7.84) and larger %FL diameter (OR = 3.88; 95% CI, 1.55-9.69) were predictive of a large PLVI decrease.Our results indicate that a larger FL and subsequent exaggerated inflammatory response may result in a trunk muscle decrease in type B AAD patients.
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Affiliation(s)
| | | | - Komei Tanaka
- Department of Cardiology, Niigata City General Hospital
| | - Yukio Hosaka
- Department of Cardiology, Niigata City General Hospital
| | | | - Hirotaka Oda
- Department of Cardiology, Niigata City General Hospital
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Wang Y, Jia X, Zhang Y, Zhang B, Zhou Y, Li X, Zhu X, Xia J, Ren J, Zou C, Zheng Q. ACKR1 hiECs Promote Aortic Dissection Through Adjusting Macrophage Behavior. Circ Res 2025; 136:211-228. [PMID: 39692014 DOI: 10.1161/circresaha.124.325458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/03/2024] [Accepted: 12/06/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development. METHODS Single-cell transcriptomic analysis of human aortic tissues was used to identify cellular heterogeneity in TAAD. Clinical and animal studies evaluated the relationship between ACKR1 expression and TAAD severity. Gain- and loss-of-function experiments, involving modulation of ACKR1 expression in ECs, investigated its role in macrophage regulation. Molecular docking and in vitro/in vivo studies identified and tested potential drugs targeting ACKR1. RESULTS TAAD tissues exhibited increased ECs with high ACKR1 expression and proinflammatory macrophages. High ACKR1 levels were strongly associated with TAAD severity. Knockdown of ACKR1 suppressed the NF-κB (nuclear factor-κB) signaling pathway and SPP1 (secreted phosphoprotein 1) expression, reducing macrophage migration and polarization, thereby inhibiting TAAD progression. Conversely, overexpression of ACKR1 exacerbated TAAD. Amikacin, identified as an ACKR1 targeted drug, regulated macrophage behavior via the ACKR1/NF-κB/SPP1 pathway, attenuating TAAD progression and improving survival in mice. CONCLUSIONS This study reveals how endothelial cells exhibiting high ACKR1 expression modulate macrophage migration and proinflammatory polarization through the ACKR1/NF-κB/SPP1 signaling pathway, a crucial mechanism in TAAD progression. Targeting ACKR1 through both functional and pharmacological approaches effectively suppressed TAAD progression and extended survival in TAAD mice, offering promising new intervention strategies for clinical evaluation.
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Affiliation(s)
- Yayu Wang
- Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Guangdong, China (Y.W., X.J., Y. Zhang, X.Z., Q.Z.)
- Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China (Y.W., X.J.)
| | - Xiong Jia
- Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Guangdong, China (Y.W., X.J., Y. Zhang, X.Z., Q.Z.)
- Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, Guangdong, China (Y.W., X.J.)
| | - Yifei Zhang
- Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Guangdong, China (Y.W., X.J., Y. Zhang, X.Z., Q.Z.)
| | - Bin Zhang
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College), Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China (B.Z., J.X., C.Z.)
| | - Yazhe Zhou
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China (Y. Zhou, X.L.)
| | - Xiaoru Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China (Y. Zhou, X.L.)
| | - Xiaoying Zhu
- Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Guangdong, China (Y.W., X.J., Y. Zhang, X.Z., Q.Z.)
| | - Jinquan Xia
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College), Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China (B.Z., J.X., C.Z.)
| | - Jun Ren
- National Clinical Research Center for Interventional Medicine, Shanghai, China (J.R.)
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China (J.R.)
| | - Chang Zou
- Department of Central Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College), Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China (B.Z., J.X., C.Z.)
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China (C.Z.)
| | - Qijun Zheng
- Department of Cardiovascular Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Guangdong, China (Y.W., X.J., Y. Zhang, X.Z., Q.Z.)
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Xie L, Lin X, Xie Y, Luo S, Wu Q, Zhang Z, Qiu Z, Chen L. The Value of Different Systemic Inflammatory Response Indicators in the Long-term Prognosis of Type B Aortic Dissection Patients Undergoing Thoracic Endovascular Aortic Repair. J Endovasc Ther 2024:15266028241305953. [PMID: 39704096 DOI: 10.1177/15266028241305953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
BACKGROUND The aim of this study is to explore the value of different systemic inflammatory response indicators in the long-term prognosis of type B aortic dissection (TBAD) patients undergoing thoracic endovascular aortic repair (TEVAR). METHODS This study retrospectively reviewed the case data of 540 patients with TBAD at our center from January 2013 to January 2019. Based on the occurrence of aorta-related adverse events (ARAEs) during follow-up, patients were divided into two groups: the ARAEs group and the non-ARAEs group. Univariate and multivariate analyses identified preoperative systemic inflammatory response index (SIRI) and C-reactive protein-to-albumin ratio (CAR) as independent risk factors for ARAEs. The SIRI-CAR score was then developed using these indicators. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal thresholds for SIRI and CAR in predicting ARAEs, then allowing for the classification of patients into high and low groups. Kaplan-Meier survival curves were used to compare survival status among patients with different SIRI, CAR, and SIRI-CAR score during follow-up, while cumulative hazard curves were used to assess the risk of various types of ARAEs among patients with differing SIRI-CAR scores. RESULTS In this study, 127 patients experienced ARAEs during follow-up. Univariate and multivariate analyses identified preoperative SIRI and CAR as independent risk factors for ARAEs. ROC curve analysis showed that the SIRI-CAR score provided superior predictive value for ARAEs compared to using SIRI and CAR separately. Kaplan-Meier survival curves revealed significantly lower ARAE-free survival rates in patients with high SIRI, high CAR, and high SIRI-CAR scores during follow-up. Additionally, cumulative hazard curves highlighted significant differences in the risk of various ARAEs among patients with different SIRI-CAR score, with the risk increasing as the score rose. CONCLUSION Preoperative SIRI and CAR are associated with the long-term prognosis of TBAD patients undergoing TEVAR, demonstrating good prognostic value. Additionally, the SIRI-CAR score, which combines both indicators, can more effectively predict the risk of long-term ARAEs. CLINICAL IMPACT This study provides valuable insights into the role of systemic inflammatory response indicators in predicting the long-term prognosis of TBAD patients undergoing TEVAR). By identifying key inflammatory biological indicators, clinicians can better stratify risk, personalize treatment, and monitor post-operative recovery more effectively. The incorporation of these indicators into clinical practice could enhance early intervention strategies, improve patient outcomes, and potentially reduce complications. The innovation lies in the focus on inflammatory responses, offering a novel prognostic tool to guide management decisions for these high-risk patients.
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Affiliation(s)
- Linfeng Xie
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Xinfan Lin
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Yuling Xie
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Siying Luo
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Qingsong Wu
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Zhaofeng Zhang
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Zhihuang Qiu
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
| | - Liangwan Chen
- Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
- Fujian Provincial Center for Cardiovascular Medicine, Fuzhou, Fujian, China
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10
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Chen P, Wei J, Ding R, Chen M, Zhao D, Li H, Chen L, Sun X, Qian X, Pu J, Chen Z, Wang L. Major adverse outcomes in patients with acute type A aortic dissection undergoing total arch replacement with frozen elephant trunk procedure. Int J Cardiol 2024; 415:132254. [PMID: 38866109 DOI: 10.1016/j.ijcard.2024.132254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 05/04/2024] [Accepted: 06/09/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND The objective of this investigation was to identify the risk factors linked to major adverse outcomes (MAO) subsequent to total arch replacement with frozen elephant trunk procedure (TAR+FET) surgery among patients diagnosed with acute type A aortic dissection (ATAAD). Additionally, the study aimed to elucidate the influence of these adverse outcomes on the long-term prognosis of the patients. METHOD 670 ATAAD patients received the TAR+FET procedure. Multivariable logistic regression was used to investigate the risk factors associated with in-hospital MAO. Additionally, long-term survival outcomes were assessed through follow-up observations of all patients. RESULTS The overall in-hospital mortality was 4.33%. Among 670 patients, 169 patients (25.22%) developed postoperative MAO. Multivariate analysis showed that in-hospital MAO was positively associated with age (OR = 1.025, 95%CI: 1.005-1.045, P = 0.014), lower limb symptoms (OR = 2.562, 95%CI: 1.407-4.666, P = 0.002), involvement of coronary artery (OR = 2.027, 95%CI: 1.312-3.130, P = 0.001), involvement of left renal artery (OR = 1.998, 95%CI: 1.359-2.938, P < 0.001), CPB time (OR = 1.011, 95%CI: 1.007-1.015, P < 0.001) and WBC counts (OR = 1.045, 95%CI: 1.007-1.083, P = 0.019). MAO group showed a worse long-term prognosis than those non-MAO group (P = 0.002). CONCLUSIONS While TAR+FET can be an effective treatment option for ATAAD patients, careful patient selection and management are essential in minimizing the risk of MAO and ensuring long-term success.
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Affiliation(s)
- Pengfei Chen
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Jinhua Wei
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Runyu Ding
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Mingjian Chen
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Diming Zhao
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Haochao Li
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Liang Chen
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Xiaogang Sun
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Xiangyang Qian
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China
| | - Jundong Pu
- Intensive Care Unit, Dali Bai Autonomous Prefecture People's Hospital, Dali, Yunnan, China
| | - Zujun Chen
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China.
| | - Liqing Wang
- Cardiovascular Surgery Department, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovescular Diseases, Beijing, China.
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11
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Huang X, Zhang G, Feng Y, Zhao X, Li Y, Liu F, Dong Y, Sun J, Xu C. Developing and Verifying an Effective Diagnostic Model Linked to Immune Infiltration in Stanford Type A Aortic Dissection. FRONT BIOSCI-LANDMRK 2024; 29:318. [PMID: 39344316 DOI: 10.31083/j.fbl2909318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 06/20/2024] [Accepted: 06/28/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND The deadly cardiovascular condition known as Stanford type A aortic dissection (TAAD) carries a high risk of morbidity and mortality. One important step in the pathophysiology of the condition is the influx of immune cells into the aorta media, which causes medial degeneration. The purpose of this work was to investigate the potential pathogenic significance of immune cell infiltration in TAAD and to test for associated biomarkers. METHODS The National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database provided the RNA sequencing microarray data (GSE153434, GPL20795, GSE52093). Immune cell infiltration abundance was predicted using ImmuCellAI. GEO2R was used to select differentially expressed genes (DEGs), which were then processed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Additionally, hub genes linked to immune infiltration were found using functional and pathway enrichment, least absolute shrinkage and selection operator (LASSO), weighted gene co-expression network analysis (WGCNA), and differential expression analysis. Lastly, hub genes were validated and assessed using receiver operating characteristic (ROC) curves in the microarray dataset GSE52093. The hub gene expression and its connection to immune infiltration in TAAD were confirmed using both animal models and clinic data. RESULTS We identified the most important connections between macrophages, T helper cell 17 (Th17), iTreg cells, B cells, natural killer cells and TAAD. And screened seven hub genes associated with immune cell infiltration: ABCG2, FAM20C, ELL2, MTHFD2, ANKRD6, GLRX, and CDCP1. The diagnostic model in TAAD diagnosis with the area under ROC (AUC) was 0.996, and the sensitivity was 99.21%, the specificity was 98.67%, which demonstrated a surprisingly strong diagnostic power of TAAD in the validation datasets. The expression pattern of four hub DEGs (ABCG2, FAM20C, MTHFD2, CDCP1) in clinic samples and animal models matched bioinformatics analysis, and ABCG2, FAM20C, MTHFD2 up-regulation, and the of CDCP1 down-regulation were also linked to poor cardiovascular function. CONCLUSIONS This study developed and verified an effective diagnostic model linked to immune infiltration in TAAD, providing new approaches to studying the potential pathogenesis of TAAD and discovering new medication intervention targets.
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Affiliation(s)
- Xiaoyan Huang
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Guoan Zhang
- Department of Cardiology Surgery, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Yangmeng Feng
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Xiangrong Zhao
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Yaping Li
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Fuqiang Liu
- Department of Cardiology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Yihan Dong
- Department of Graduate School, Yan'an University, 716000 Yan'an, Shaanxi, China
| | - Jingying Sun
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
| | - Cuixiang Xu
- Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
- Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, 710068 Xi'an, Shaanxi, China
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12
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Xu S, Han X, Wang X, Yu Y, Qu C, Liu X, Yang B. The role of oxidative stress in aortic dissection: a potential therapeutic target. Front Cardiovasc Med 2024; 11:1410477. [PMID: 39070552 PMCID: PMC11272543 DOI: 10.3389/fcvm.2024.1410477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 07/01/2024] [Indexed: 07/30/2024] Open
Abstract
The incidence of aortic dissection (AD) is steadily increasing, driven by the rising prevalence of chronic conditions such as hypertension and the global aging of the population. Oxidative stress emerges as a pivotal pathophysiological mechanism contributing to the progression of AD. Oxidative stress triggers apoptosis in vascular smooth muscle cells, reshapes the extracellular matrix (ECM), and governs ECM degradation and remodeling, subsequently impacting aortic compliance. Furthermore, oxidative stress not only facilitates the infiltration of macrophages and mononuclear lymphocytes but also disrupts the integral structure and functionality of endothelial cells, thereby inducing endothelial cell dysfunction and furthering the degeneration of the middle layer of the aortic wall. Investigating antioxidants holds promise as a therapeutic avenue for addressing AD.
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Affiliation(s)
- Shengnan Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Xueyu Han
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Xiukun Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Yi Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Chuan Qu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Xin Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
| | - Bo Yang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Hubei Key Laboratory of Cardiology, Wuhan University, Wuhan, China
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13
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Wu Q, Zheng J, Lin J, Xie L, Tang M, Ke M, Chen L. Preoperative blood urea nitrogen-to-serum albumin ratio for prediction of in-hospital mortality in patients who underwent emergency surgery for acute type A aortic dissection. Hypertens Res 2024; 47:1934-1942. [PMID: 38769137 PMCID: PMC11224014 DOI: 10.1038/s41440-024-01673-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 02/26/2024] [Accepted: 03/17/2024] [Indexed: 05/22/2024]
Abstract
The study aimed to assess the predictive value of blood urea nitrogen (BUN)-to-albumin ratio (BA-R) for in-hospital mortality in patients undergoing emergency surgery for acute type A aortic dissection (ATAAD). Patients who were diagnosed with ATAAD and underwent emergency surgery within 48 hours of onset at our hospital between January 2015 and December 2021 were included in this study. The primary endpoint of this study was postoperative in-hospital mortality (POIM). The data of the survivors and non-survivors were retrospectively compared analyses. A total of 557 ATAAD patients were included, with 505 survivors and 52 non-survivors. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (P < 0.001). Univariate regression analysis showed that preoperative BA-R, serum creatinine level, SA level, D-dimer level, age, myocardial ischemia, cerebral ischemia, and aortic clamp time were risk factors for POIM. In addition, multivariable regression analysis showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). Receiver operating characteristic curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (area under the curve =0.874). The sensitivity and specificity of preoperative BA-R in predicting the POIM of patients who underwent emergency surgery for ATAAD were 84.6% and 71.3%, respectively (95% confidence interval, 0.829-0.919; P < 0.001). In conclusion, Preoperative BA-R is a simple, rapid, and potentially useful prognostic indicator of POIM in patients with ATAAD. BAR: Blood urea nitrogen-to-albumin ratio, BUN: Blood urea nitrogen, SA: Serum albumin, REF: Reference. The aim of this study was to evaluate the prognostic value of BA-R for the prediction of postoperative in-hospital mortality in patients who underwent emergency surgery for ATAAD. A total of 557 patients with ATAAD were enrolled, and 505 survived while 52 did not. The preoperative BA-R of the non-survivor group was significantly higher than that of the survivor group (0.27 [0.18, 0.46] vs. 0.12 [0.10, 0.16]mmol/g; P < 0.001). The study showed that preoperative BA-R ≥ 0.155 mmol/g was a risk factor for POIM (odds ratio, 6.815 [3.582-12.964]; P < 0.001). ROC curve indicated that the cut-off point for preoperative BA-R was ≥0.155 mmol/g (AUC = 0.874) and the sensitivity and specificity were 84.6% and 71.3%, respectively (95% CI, 0.829-0.919; P < 0.001). We believe that our study makes a significant contribution to the literature because we found preoperative BA-R to be a simple, rapid, and potentially useful prognostic indicator of postoperative in-hospital mortality in patients with ATAAD.
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Affiliation(s)
- Qingsong Wu
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, P. R. China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, 350001, P. R. China
| | - Jian Zheng
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, P. R. China
| | - Jianling Lin
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, P. R. China
| | - Linfeng Xie
- Fujian Medical University, Fuzhou, Fujian, P. R. China
| | - Mirong Tang
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, P. R. China
| | - Meng Ke
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, P. R. China.
| | - Liangwan Chen
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian, P. R. China.
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, 350001, P. R. China.
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14
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Huang M, Lian Y, Zeng Z, Li J. D-dimer, C-reactive protein and matrix metalloproteinase 9 for prediction of type A aortic dissection patient survival. ESC Heart Fail 2024; 11:147-154. [PMID: 37849442 PMCID: PMC10804169 DOI: 10.1002/ehf2.14552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 08/29/2023] [Accepted: 09/20/2023] [Indexed: 10/19/2023] Open
Abstract
AIMS Acute type A aortic dissection (ATAAD) is a life-threatening condition requiring prompt diagnosis and treatment. Surgery is an effective treatment for ATAAD, but the in-hospital mortality rate in the 30 day perioperative period is still as high as 9-30%. It is critical to identify biological factors for preoperative assessment of post-operative survival in patients with ATAAD. METHODS AND RESULTS This is a retrospective study, investigating the association of combined measurements of d-dimer, C-reactive protein (CRP), and matrix metalloproteinase 9 (MMP9) for 1 year of survival in patients with ATAAD. Data from 247 patients who underwent surgery were analysed, including 89 patients who did not survive and 158 patients who survived within 1 year after surgery. Pearson's correlation analysis was carried out to determine the correlations between CRP in whole blood, d-dimer in plasma, and CRP in whole blood. Receiver operating characteristic (ROC) analysis was used to analyse the value of preoperative whole blood CRP, plasma d-dimer, and serum MMP9 concentration and the combined detection model in predicting death of patients with ATAAD. Deceased patients with ATAAD exhibited higher age, hypertension prevalence, systolic blood pressure, white blood cell count, whole blood CRP, plasma d-dimer, and serum MMP9 levels compared with survivors. Preoperative CRP, d-dimer, and MMP9 levels were significantly higher in patients with ATAAD compared with healthy controls. Positive correlations were observed between CRP and d-dimer, CRP and MMP9, and d-dimer and MMP9 in patients with ATAAD. ROC analysis showed that the combined detection model of CRP, d-dimer, and MMP9 had the highest predictive value for 1 year of survival (area under the curve = 0.88). CONCLUSIONS Combined measurement of CRP, d-dimer, and MMP9 is associated with 1 year of survival in patients with ATAAD.
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Affiliation(s)
- Minjie Huang
- Department of Vascular SurgeryQuanzhou First Hospital Affiliated to Fujian Medical UniversityFujian East StreetQuanzhou362000FujianChina
| | - Yujie Lian
- Department of Vascular SurgeryQuanzhou First Hospital Affiliated to Fujian Medical UniversityFujian East StreetQuanzhou362000FujianChina
| | - Zhongyan Zeng
- Department of Vascular SurgeryQuanzhou First Hospital Affiliated to Fujian Medical UniversityFujian East StreetQuanzhou362000FujianChina
| | - Jiahong Li
- Department of Vascular SurgeryQuanzhou First Hospital Affiliated to Fujian Medical UniversityFujian East StreetQuanzhou362000FujianChina
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Zong J, Yang L, Wei L, Wang D, Wang X, Zhang Z. MALT1 Positively Relates to T Helper 1 and T Helper 17 cells, and Serves as a Potential Biomarker for Predicting 30-Day Mortality in Stanford Type A Aortic Dissection Patients. TOHOKU J EXP MED 2023; 261:299-307. [PMID: 37704417 DOI: 10.1620/tjem.2023.j077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
Mucosa-associated lymphoid tissue 1 (MALT1) regulates inflammation and T helper (Th) cell differentiation, which may participate in the progression of Stanford type A aortic dissection (TAAD). This study intended to assess the association of MALT1 expression with prognosis in TAAD patients. In this prospective study, MALT1 expression was measured by reverse transcription-quantitative polymerase chain reaction assay from peripheral blood samples in 100 TAAD patients and 100 non-AD controls (non-AD patients with chest pain) before treatment. Besides, Th1, Th2, and Th17 cells of TAAD patients before treatment were measured by flow cytometry assay, and their 30-day mortality was recorded. MALT1 expression was ascended in TAAD patients vs. non-AD controls (P < 0.001). In TAAD patients, elevated MALT1 expression was linked with hypertension complication (P = 0.009), increased systolic blood pressure (r = 0.291, P = 0.003), C-reactive protein (CRP) (r = 0.286, P = 0.004), and D-dimer (r = 0.359, P < 0.001). Additionally, MALT1 expression was positively correlated with Th1 cells (r = 0.312, P = 0.002) and Th17 cells (r = 0.397, P < 0.001), but not linked with Th2 cells (r = -0.166, P = 0.098). Notably, the 30-day mortality of TAAD patients was 28.0%. MALT1 expression [odds ratio (OR) = 1.936, P = 0.004], CRP (OR = 1.108, P = 0.002), D-dimer (OR = 1.094, P = 0.003), and surgery timing (emergency vs. selective) (OR = 8.721, P = 0.024) independently predicted increased risk of death within 30 days in TAAD patients. Furthermore, the combination of the above-mentioned independent factors had an excellent ability in predicting 30-day mortality with the area under curve of 0.949 (95% confidence interval: 0.909-0.989). MALT1 expression relates to increased Th1 cells, Th17 cells, and 30-day mortality risk in TAAD patients.
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Affiliation(s)
- Junqing Zong
- Department of Cardiovascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University
| | - Lingbo Yang
- Department of Cardiovascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University
| | - Lei Wei
- Department of Cardiovascular Surgery, Shanxi Provincial People's Hospital
| | - Dong Wang
- Department of Cardiovascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University
| | - Xuening Wang
- Department of Cardiovascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University
| | - Zhongjie Zhang
- Department of Cardiovascular Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University
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Zhang Z, Wang L, Su X, Zhou Y, Wu K, Sun G, Ou W, Yu L, Chen W, Wang B. Analysis of clinical characteristics and imagological features of the aortic dissection patients with negative D-dimer results. Front Cardiovasc Med 2023; 10:1266919. [PMID: 38107258 PMCID: PMC10722295 DOI: 10.3389/fcvm.2023.1266919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 11/15/2023] [Indexed: 12/19/2023] Open
Abstract
Background D-dimer (DD) is a vital biomarker to rule out the diagnosis of aortic dissection (AD). However, the DD level in some patients with AD is not high in clinical practice, which often leads to missed diagnosis; therefore, understanding the characteristics of patients with AD and negative DD is of great clinical value. Methods From May 2015 to October 2020, 286 patients with AD who visited the first medical contact (FMC) within 24 h of symptom onset and were hospitalized in the Xiamen Cardiovascular Hospital of Xiamen University were enrolled in this study. Clinical characteristics and outcomes of patients were assessed. Results Among them, 13 cases (approximately 4.5%) had negative DD results. Compared to patients with positive DD results, patients with negative DD results had significantly higher platelet counts and lower aortic dissection detection risk scores (ADD-RS). The imagological analysis showed that patients with AD and negative DD had lower extension scores and milder damage to the mesenteric artery and three branches of the aortic arch. Furthermore, the results of the multivariable analysis showed that white blood cell count (WBC) [odds ratio (OR): 1.379, P = 0.028], FMC (OR: 0.904, P = 0.028), and extension score (OR: 1.623, P = 0.046) were associated with negative DD result. Conclusions Patients with AD and negative DD results had longer FMC and lower WBC. Imaging showed a smaller tear extension range and less damage to the mesenteric artery and three branches of the aortic arch. A negative DD result could not completely rule out AD even if the ADD-RS was zero.
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Affiliation(s)
- Zhixiang Zhang
- Department of Emergency, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Lilan Wang
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Xin Su
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Yuling Zhou
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Kaimin Wu
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Guangfeng Sun
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Weimei Ou
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Lihong Yu
- Department of Emergency, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Weifen Chen
- The Third Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Bin Wang
- Department of Emergency, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
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Chen C, Gao L, Ge H, Huang W, Zhao R, Gu R, Li Z, Wang X. A neural network model was constructed by screening the potential biomarkers of aortic dissection based on genes associated with pyroptosis. Aging (Albany NY) 2023; 15:12388-12399. [PMID: 37938149 PMCID: PMC10683593 DOI: 10.18632/aging.205187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 10/08/2023] [Indexed: 11/09/2023]
Abstract
BACKGROUND Aortic dissection (AD) is one of the crucial and common cardiovascular diseases, and pyroptosis is a novel cell delivery mechanism that is probably involved in the pathogenesis of various cardiovascular diseases. However, no study has investigated the role of pyroptosis in AD. METHODS We obtained two AD datasets, GSE153434 and GSE190635, from the Gene Expression Omnibus database. The differential expression of AD-related genes was determined by differential analysis, and their enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Additionally, a protein-protein interaction network was established. Next, potential biomarkers were screened by Lasso regression analysis, and a neural network model was constructed. Finally, the potential biomarkers were validated by constructing a mouse model of AD. RESULTS A total of 1033 differentially expressed related genes were distinguished and these genes were mainly associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase signaling pathways. The Lasso regression results showed five potential biomarkers, namely platelet endothelial cell adhesion molecule-1 (PECAM1), caspase 4 (CASP4), mixed lineage kinase domain-like pseudokinase (MLKL), APAF1-interacting protein (APIP), and histone deacetylase 6 (HDAC6) and successfully constructed a neural network model to predict AD occurrence. The results showed that CASP4 and MLKL were highly expressed, whereas PECAM1 and HDAC6 were lowly expressed in AD samples, and no statistically significant difference was observed in APIP expression in AD samples. CONCLUSION Pyroptosis plays a crucial role in AD occurrence and development. Moreover, the five potential biomarkers identified in the present study can act as targets for the early diagnosis of AD in patients.
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Affiliation(s)
- Cheng Chen
- Department of Vascular Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
| | - Lulu Gao
- Department of Anesthesiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
| | - Hongwei Ge
- Department of Vascular Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
| | - Weibin Huang
- Department of Vascular Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
| | - Rong Zhao
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
| | - Renjun Gu
- School of Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Ziyun Li
- School of Acupuncture and Tuina, School of Regimen and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xin Wang
- Department of Vascular Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213000, China
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Huang M, Guan R, Qiu J, Gnamey AJE, Wang Y, Tian H, Sun H, Shi H, Sun W, Jia X, Wu J. Identification of immune-related signatures and pathogenesis differences between thoracic aortic aneurysm patients with bicuspid versus tricuspid valves via weighted gene co-expression network analysis. PLoS One 2023; 18:e0292673. [PMID: 37883426 PMCID: PMC10602290 DOI: 10.1371/journal.pone.0292673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 09/26/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND Thoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients. METHODS Publically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets. RESULTS WGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association. CONCLUSIONS TAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.
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Affiliation(s)
- Min Huang
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Rong Guan
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Jiawei Qiu
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Abla Judith Estelle Gnamey
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Yusi Wang
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Hai Tian
- Future Medical Laboratory, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Haoran Sun
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Hongbo Shi
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Wenjing Sun
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Xueyuan Jia
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
| | - Jie Wu
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
- Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, Heilongjiang, China
- Future Medical Laboratory, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Sheng Y, Wu L, Chang Y, Liu W, Tao M, Chen X, Zhang X, Li B, Zhang N, Ye D, Zhang C, Zhu D, Zhao H, Chen A, Chen H, Song J. Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection. BMC Med 2023; 21:396. [PMID: 37858098 PMCID: PMC10588060 DOI: 10.1186/s12916-023-03077-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 09/11/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.
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Affiliation(s)
- Yixuan Sheng
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Liying Wu
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuan Chang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Wendao Liu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Menghao Tao
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Xiao Chen
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Xiong Zhang
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Bin Li
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Ningning Zhang
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Dongting Ye
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chunxi Zhang
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Daliang Zhu
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Haisen Zhao
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Aijun Chen
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Haisheng Chen
- Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
| | - Jiangping Song
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
- Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, 518057, China.
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Xu H, Wang H, Wu L, Xu T, Han L, Lu F, Li B, Sun Y, Xu Z. Prognostic Value of Systemic Inflammation Response Index in Acute Type A Aortic Dissection. World J Surg 2023; 47:2554-2561. [PMID: 37244873 DOI: 10.1007/s00268-023-07079-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2023] [Indexed: 05/29/2023]
Abstract
BACKGROUND The study aimed to evaluate the prognostic value of preoperative systemic inflammation response index (SIRI) for acute type A aortic dissection (ATAD) following open surgery. METHODS AND RESULTS Totally, 410 ATAD patients underwent open surgery from 2019 to 2021 were enrolled in the study. Among the patients, the in-hospital mortality was 14.4%. Cox regression (95%CI 1.033-1.114p < 0.001) and receiver operating characteristic curve analysis (AUC = 0.718, p < 0.001) demonstrated the prognostic role of SIRI for in-hospital mortality after surgery. The optimal cut-off value of SIRI for in-hospital mortality was identified as 9.43 by maximally selected Log-Rank statistics. The patients were divided into high SIRI group (SIRI ≥ 9.43) and low SIRI group (SIRI < 9.43)) after the linear inverse relationship between SIRI and hazard ratio for in-hospital mortality was demonstrated by restricted cubic spline analysis (p = 0.0742). The Kaplan-Meier analysis illustrated that in-hospital mortality increased significantly in high SIRI group (p < 0.001). In addition, elevating SIRI was significantly associated with the incidence of coronary sinus tear (95%CI 1.020-4.475p = 0.044). Furthermore, the incidence rate of postoperative complications including renal failure (p < 0.001) and infection (p = 0.019) was higher in high SIRI group. CONCLUSION The study indicated that preoperative SIRI could provide strong prognostic value for in-hospital mortality in ATAD patients following open surgery. Thus, SIRI was a promising biomarker for risk stratification and management prior to open surgery.
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Affiliation(s)
- Hongjie Xu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - He Wang
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Lujia Wu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Tianyu Xu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Lin Han
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Fanglin Lu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Bailing Li
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
| | - Yangyong Sun
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China.
| | - Zhiyun Xu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
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Wang MM, Gai MT, Wang BZ, Yesitayi G, Ma YT, Ma X. A prediction model to predict in-hospital mortality in patients with acute type B aortic dissection. BMC Cardiovasc Disord 2023; 23:257. [PMID: 37198546 DOI: 10.1186/s12872-023-03260-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 04/25/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Acute type B aortic dissection (ABAD) is a life-threatening cardiovascular disease. A practicable and effective prediction model to predict and evaluate the risk of in-hospital death for ABAD is required. The present study aimed to construct a prediction model to predict the risk of in-hospital death in ABAD patients. METHODS A total of 715 patients with ABAD were recruited in the first affiliated hospital of Xinjiang medical university from April 2012 to May 2021. The information on the demographic and clinical characteristics of all subjects was collected. The logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and nomogram were applied to screen the appropriate predictors and to establish a prediction model for the risk of in-hospital mortality in ABAD. The receiver operator characteristic curve and calibration plot were applied to validate the performance of the prediction model. RESULTS Of 53 (7.41%) subjects occurred in-hospital death in 715 ABAD patients. The variables including diastolic blood pressure (DBP), platelets, heart rate, neutrophil-lymphocyte ratio, D-dimer, C-reactive protein (CRP), white blood cell (WBC), hemoglobin, lactate dehydrogenase (LDH), procalcitonin, and left ventricular ejection fraction (LVEF) were shown a significant difference between the in-hospital death group and the in-hospital survival group (all P < 0.05). Furthermore, all these factors which existed differences, except CRP, were associated with in-hospital deaths in ABAD patients (all P < 0.05). Then, parameters containing LVEF, WBC, hemoglobin, LDH, and procalcitonin were identified as independent risk factors for in-hospital deaths in ABAD patients by adjusting compound variables (all P < 0.05). In addition, these independent factors were qualified as predictors to build a prediction model (AUC > 0.5, P < 0.05). The prediction model was shown a favorable discriminative ability (C index = 0.745) and demonstrated good consistency. CONCLUSIONS The novel prediction model combined with WBC, hemoglobin, LDH, procalcitonin, and LVEF, was a practicable and valuable tool to predict in-hospital deaths in ABAD patients.
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Affiliation(s)
- Meng-Meng Wang
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China
| | - Min-Tao Gai
- Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China
- Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi, 830011, China
| | - Bao-Zhu Wang
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Gulinazi Yesitayi
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yi-Tong Ma
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
- Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China.
| | - Xiang Ma
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
- Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China.
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Lin Q, Wu Q, Chen X, Chen X, Xie L, Chen L. Seasonal and daily variations in the occurence and outcomes of acute Stanford type A dissections: a retrospective single-center study. J Cardiothorac Surg 2023; 18:108. [PMID: 37029426 PMCID: PMC10080959 DOI: 10.1186/s13019-023-02222-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 04/02/2023] [Indexed: 04/09/2023] Open
Abstract
BACKGROUND To investigate the seasonal, monthly, and daily distributions of the incidence of Stanford type-A acute aortic dissection (TAAAD) and identify seasonality in the duration of hospital stay and in-hospital mortality of TAAAD in south-eastern China. METHODS We enrolled patients diagnosed with TAAAD between 1 June 2017 and 31 May 2021. Participants were divided into seasonal, monthly, and daily groups according to the need for analysis. Analysis of variance was applied to compare the number of TAAAD in different seasons, months, and days. χ2 test was used to compare in-hospital mortality among the four groups. Non-parametric methods were used for all comparisons of the duration of hospital stay. Univariate logistic and multivariable logistic regression analyses were performed to assess the duration of hospital stay. RESULTS Of the 485 patients, 154 were diagnosed in winter (31.8%), 115 in spring (23.7%), 73 in summer (15.1%), and 143 in autumn (29.5%). The daily, monthly, and seasonal distributions of TAAAD were significantly different (P = 0.04, P < 0.01, and P < 0.01, respectively). This study did not identify any significant decrease in maximal, mean, or minimum temperatures between the three days before TAAAD and the day of TAAAD. No seasonal variations associated with in-hospital mortality was observed (P = 0.89). However, significant differences were observed in the seasonal distribution of the duration of hospital stay for TAAAD [winter was 17.0 (4.0-24.0) days, spring was 20.0 (14.0-29.0) days, summer was 20.0 (12.5-31.0) days, and autumn was 20.0 (13.0-30.0) days, P < 0.01]. Multiple factor analysis showed that winter was the independent risk factor for the increased duration of hospital stay. The odds ratio for winter was 2.21 (1.46, 3.33, P < 0.01). CONCLUSIONS Our study confirmed that the incidence of TAAAD exhibits seasonal, monthly, and daily variations in south-eastern China. Moreover, the daily incidence of TAAAD is higher on weekdays than that on weekends.
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Affiliation(s)
- Qinmei Lin
- Department of Outpatient, Union Hospital, Fujian Medical University, Fuzhou, Fujian, People's Republic of China
| | - Qingsong Wu
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Xinquan Road 29, Fuzhou, Fujian, People's Republic of China
- Fujian Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, 350001, Fujian, People's Republic of China
- Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, People's Republic of China
| | - Xiaodong Chen
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Xinquan Road 29, Fuzhou, Fujian, People's Republic of China
| | - Xingfeng Chen
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Xinquan Road 29, Fuzhou, Fujian, People's Republic of China
| | - Linfeng Xie
- Fujian Medical University, Fuzhou, Fujian, People's Republic of China
| | - Liangwan Chen
- Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Xinquan Road 29, Fuzhou, Fujian, People's Republic of China.
- Fujian Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, 350001, Fujian, People's Republic of China.
- Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, People's Republic of China.
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Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection. Biomolecules 2023; 13:biom13020399. [PMID: 36830768 PMCID: PMC9952989 DOI: 10.3390/biom13020399] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/26/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023] Open
Abstract
Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.
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Liang Q, Zhou Z, Li H, Tao Q, Wang Y, Lin A, Xu J, Zhang B, Wu Y, Min H, Wang L, Song S, Wang D, Gao Q. Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection. Front Cardiovasc Med 2023; 9:1074835. [PMID: 36712253 PMCID: PMC9880160 DOI: 10.3389/fcvm.2022.1074835] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/21/2022] [Indexed: 01/15/2023] Open
Abstract
Introduction Stanford type A aortic dissection (TAAD) is one of the lethal macrovascular diseases caused by the invasion of blood into the media layer of ascending aortic wall. Inflammation, smooth muscle dysfunction, and extracellular matrix (ECM) degradation were regarded as the major pathology in affected tissue. However, the expression pattern and its regulation especially through circular RNAs (circRNAs) as an overall characteristic of TAAD molecular pathology remain unclear. Methods We employed CIRCexplorer2 to identify circRNAs based on the RNA sequencing (RNA-seq) data of human ascending aortic tissues to systematically assess the role of circRNA in the massive alterations of gene expression in TAAD aortas. The key circRNAs were determined by LASSO model and functionally annotated by competing endogenous RNAs (ceRNA) network and co-analysis with mRNA profile. The expression level and diagnostic capability of the 4 key circRNAs in peripheral serum were confirmed by real-time polymerase chain reaction (RT-PCR). Results The 4 key circRNAs, namely circPTGR1 (chr9:114341075-114348445[-]), circNOX4 (chr11:89069012-89106660[-]), circAMN1 (chr12:31854796-31862359[-]) and circUSP3 (chr15:63845913-63855207[+]), demonstrated a high power to discriminate between TAAD and control tissues, suggesting that these molecules stand for a major difference between the tissues at gene regulation level. Functionally, the ceRNA network of circRNA-miRNA-mRNA predicted by the online databases, combining gene set enrichment analysis (GSEA) and cell component prediction, revealed that the identified circRNAs covered all the aspects of primary TAAD pathology, centralized with increasing inflammatory factors and cells, and ECM destruction and loss of vascular inherent cells along with the circRNAs. Importantly, we validated the high concentration and diagnostic capability of the 4 key circRNAs in the peripheral serum in TAAD patients. Discussion This study reinforces the vital status of circRNAs in TAAD and the possibility of serving as promising diagnostic biomarkers.
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Affiliation(s)
- Qiao Liang
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Zeyi Zhou
- Department of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Hui Li
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Qing Tao
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Yali Wang
- Department of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Anqi Lin
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Jing Xu
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Bin Zhang
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China,Central Laboratory, Nanjing Chest Hospital, Nanjing Medical University, Nanjing, China
| | - Yongzheng Wu
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Haiyan Min
- Central Laboratory, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Wang
- Department of Clinical Laboratory, Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
| | - Shiyu Song
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Dongjin Wang
- Department of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China,*Correspondence: Qian Gao ✉
| | - Qian Gao
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, China,Dongjin Wang ✉
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25
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Ma M, Zhu F, Fan F, Pan J, Cao H, Zhou Q, Wang D. Relationship between preoperative lymphocyte to monocyte ratio and surgery outcome in type A aortic dissection. Front Surg 2023; 9:1103290. [PMID: 36684141 PMCID: PMC9849739 DOI: 10.3389/fsurg.2022.1103290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 12/12/2022] [Indexed: 01/07/2023] Open
Abstract
Background Lymphocyte-to-monocyte ratio (LMR) is associated with the mortality of cardiovascular diseases. However, the relationship between preoperative LMR and the prognosis of patients with Stanford type A aortic dissection (TAAD) undergoing surgical treatment remains to be determined. Methods We enrolled 879 patients with TAAD undergoing surgical treatment between January 2018 and December 2021. Patients were divided into two groups: the Deceased group and the Survived group. The baseline clinical and operative characteristics of the two groups were compared and analyzed. Results In univariate and multivariate logistic regression analysis, the association between LMR and in-hospital mortality was significant, and LMR (OR = 1.598, 95% CI 1.114-2.485, P = 0.022) remained significant after adjusting for confounders. Conclusion Lower LMR may be independently associated with higher in-hospital mortality in TAAD undergoing surgical treatment.
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Affiliation(s)
- Ming Ma
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Feng Zhu
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Fudong Fan
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Jun Pan
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Hailong Cao
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Qing Zhou
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Dongjin Wang
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China,Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China,Correspondence: Dongjin Wang
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26
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Pan T, Tuoerxun T, Chen X, Yang CJ, Jiang CY, Zhu YF, Li ZS, Jiang XY, Zhang HT, Zhang H, Wang YP, Chen W, Lu LC, Ge M, Cheng YQ, Wang DJ, Zhou Q. The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass. Front Immunol 2023; 14:1082830. [PMID: 36761773 PMCID: PMC9902923 DOI: 10.3389/fimmu.2023.1082830] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 01/09/2023] [Indexed: 01/26/2023] Open
Abstract
Background The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery. Methods Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc. Results In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01). Conclusion Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB. Registration http://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.
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Affiliation(s)
- Tuo Pan
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Tayierjiang Tuoerxun
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xi Chen
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Cheng-Jin Yang
- Department of Pediatric Surgery, Sanya Women and Children's Hospital, Sanya, China
| | - Chen-Yu Jiang
- Department of Cardio-Thoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yi-Fan Zhu
- Department of Cardio-Thoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ze-Shi Li
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Xin-Yi Jiang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Hai-Tao Zhang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - He Zhang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Ya-Peng Wang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Wei Chen
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Li-Chong Lu
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Min Ge
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Yong-Qing Cheng
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Dong-Jin Wang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, China
| | - Qing Zhou
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
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27
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Yu D, Chen P, Zhang X, Wang H, Dhuromsingh M, Wu J, Qin B, Guo S, Zhang B, Li C, Zeng H. Association of lymphopenia and RDW elevation with risk of mortality in acute aortic dissection. PLoS One 2023; 18:e0283008. [PMID: 36920980 PMCID: PMC10016706 DOI: 10.1371/journal.pone.0283008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 02/28/2023] [Indexed: 03/16/2023] Open
Abstract
OBJECTIVE The study aimed to investigate whether lymphopenia and red blood cell distribution width (RDW) elevation are associated with an increased risk of mortality in acute aortic dissection (AAD). METHODS This multicenter retrospective cohort study enrolled patients diagnosed with AAD by aortic computed tomographic angiography (CTA) from 2010 to 2021 in five teaching hospitals in central-western China. Cox proportional hazards regression and Kaplan-Meier curves were used in univariable and multivariable models. Clinical outcomes were defined as all-cause in-hospital mortality, while associations were evaluated between lymphopenia, accompanied by an elevated RDW, and risk of mortality. RESULTS Of 1903 participants, the median age was 53 (interquartile range [IQR], 46-62) years, and females accounted for 21.9%. Adjusted increased risk of mortality was linearly related to the decreasing lymphocyte percentage (P-non-linearity = 0.942) and increasing RDW (P-non-linearity = 0.612), and per standard deviation (SD) of increment lymphocyte percentage and RDW was associated with the 26% (0.74, 0.64-0.84) decrement and 5% (1.05, 0.95-1.15) increment in hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality, respectively. Importantly, lymphopenia and elevation of RDW exhibited a significant interaction with increasing the risk of AAD mortality (P-value for interaction = 0.037). CONCLUSIONS Lymphopenia accompanied by the elevation of RDW, which may reflect the immune dysregulation of AAD patients, is associated with an increased risk of mortality. Assessment of immunological biomarkers derived from routine tests may provide novel perspectives for identifying the risk of mortality.
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Affiliation(s)
- Dan Yu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, China
- Department of Cardiac Intensive Care Unit, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, China
| | - Peng Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueyan Zhang
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, China
| | - Hongjie Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, China
| | - Menaka Dhuromsingh
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, China
| | - Jinxiu Wu
- Department of Critical Care Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Bingyu Qin
- Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, China
- * E-mail: (BQ); (SG); (BZ); (CL); (HZ)
| | - Suping Guo
- Department of Cardiac Intensive Care Unit, People’s Hospital of Zhengzhou University (Henan Provincial People’s Hospital), Zhengzhou, China
- Department of Cardiac Intensive Care Unit, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), Zhengzhou, China
- * E-mail: (BQ); (SG); (BZ); (CL); (HZ)
| | - Baoquan Zhang
- Department of Critical Care Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
- * E-mail: (BQ); (SG); (BZ); (CL); (HZ)
| | - Chunwen Li
- Department of Emergency Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- * E-mail: (BQ); (SG); (BZ); (CL); (HZ)
| | - Hesong Zeng
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, China
- * E-mail: (BQ); (SG); (BZ); (CL); (HZ)
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28
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Ainiwan M, Wang Q, Yesitayi G, Ma X. Identification of FERMT1 and SGCD as key marker in acute aortic dissection from the perspective of predictive, preventive, and personalized medicine. EPMA J 2022; 13:597-614. [PMID: 36505894 PMCID: PMC9727066 DOI: 10.1007/s13167-022-00302-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/25/2022] [Indexed: 11/16/2022]
Abstract
Acute aortic dissection (AAD) is a severe aortic injury disease, which is often life-threatening at the onset. However, its early prevention remains a challenge. Therefore, in the context of predictive, preventive, and personalized medicine (PPPM), it is particularly important to identify novel and powerful biomarkers. This study aimed to identify the key markers that may contribute to the predictive early risk of AAD and analyze their role in immune infiltration. Three datasets, including a total of 23 AAD and 20 healthy control aortic samples, were retrieved from the Gene Expression Omnibus (GEO) database, and a total of 519 differentially expressed genes (DEGs) were screened in the training set. Using the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) algorithm, FERMT1 (AUC = 0.886) and SGCD (AUC = 0.876) were identified as key markers of AAD. A novel AAD risk prediction model was constructed using an artificial neural network (ANN), and in the validation set, the AUC = 0.920. Immune infiltration analysis indicated differential gene expression in regulatory T cells, monocytes, γδ T cells, quiescent NK cells, and mast cells in the patients with AAD and the healthy controls. Correlation and ssGSEA analysis showed that two key markers' expression in patients with AAD was correlated with many inflammatory mediators and pathways. In addition, the drug-gene interaction network identified motesanib and pyrazoloacridine as potential therapeutic agents for two key markers, which may provide personalized medical services for AAD patients. These findings highlight FERMT1 and SGCD as key biological targets for AAD and reveal the inflammation-related potential molecular mechanism of AAD, which is helpful for early risk prediction and targeted prevention of AAD. In conclusion, our study provides a new perspective for developing a PPPM method for managing AAD patients. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-022-00302-4.
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Affiliation(s)
- Mierxiati Ainiwan
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi, 830000 China
| | - Qi Wang
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi, 830000 China
| | - Gulinazi Yesitayi
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi, 830000 China
| | - Xiang Ma
- Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi, 830000 China
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29
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Zheng B, Huang XQ, Chen Z, Wang J, Gu GF, Luo XJ. Aortic dissection with epileptic seizure: A case report. World J Clin Cases 2022; 10:11542-11548. [PMID: 36387786 PMCID: PMC9649543 DOI: 10.12998/wjcc.v10.i31.11542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/30/2022] [Accepted: 10/09/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Aortic dissection (AoD) is a life-threatening disease. Its diversified clinical manifestations, especially the atypical ones, make it difficult to diagnose. The epileptic seizure is a neurological problem caused by various kinds of diseases, but AoD with epileptic seizure as the first symptom is rare.
CASE SUMMARY A 53-year-old male patient suffered from loss of consciousness for 1 h and tonic-clonic convulsion for 2 min. The patient performed persistent hypomania and chest discomfort for 30 min after admission. He had a history of hypertension without regular antihypertensive drugs, and the results of his bilateral blood pressure varied greatly. Then the electroencephalogram showed the existence of epileptic waves. The thoracic aorta computed tomography angiography showed the appearance of AoD, and it originated at the lower part of the ascending aorta. Finally, the diagnosis was AoD (DeBakey, type I), acute aortic syndrome, hypertension (Grade 3), and secondary epileptic seizure. He was given symptomatic treatment to relieve symptoms and prevent complications. Thereafter, the medical therapy was effective but he refused our surgical advice.
CONCLUSION The AoD symptoms are varied. When diagnosing the epileptic seizure etiologically, AoD is important to consider by clinical and imaging examinations.
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Affiliation(s)
- Bo Zheng
- Department of Neurology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
| | - Xue-Qiong Huang
- Department of Oncology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
| | - Zhao Chen
- Department of Neurology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
| | - Jian Wang
- Department of Neurology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
| | - Gang-Feng Gu
- Department of Neurology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
| | - Xiao-Jing Luo
- Department of Neurology, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
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30
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Kim DH. Toward an Easily Obtainable Novel Biomarker for Type A Dissection? JACC. ASIA 2022; 2:777-779. [PMID: 36444324 PMCID: PMC9699999 DOI: 10.1016/j.jacasi.2022.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Affiliation(s)
- Dae-Hee Kim
- Cardiac Imaging Center, Asan Medical Center Heart Institute, University of Ulsan College of Medicine, Seoul, South Korea
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31
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Liu H, Qian SC, Shao YF, Li HY, Zhang HJ, 5A Investigators. Prognostic Impact of Systemic Coagulation-Inflammation Index in Acute Type A Aortic Dissection Surgery. JACC. ASIA 2022; 2:763-776. [PMID: 36444319 PMCID: PMC9700012 DOI: 10.1016/j.jacasi.2022.06.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND A novel hematologic parameter, systemic coagulation-inflammation (SCI) index reflecting inflammation and coagulation pathways could be easily obtained from clinically routine laboratory findings. We hypothesize that the SCI index has prognostic implication in predicting operative mortality for patients with acute type A aortic dissection (ATAAD). OBJECTIVES This study aims to investigate the prognostic value of the SCI index and to establish an SCI-adding nomogram for mortality prediction in ATAAD patients. METHODS A total of 1,967 ATAAD patients surgically repaired were collected from 12 Chinese cardiovascular centers by the 5A (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [Multicenter Retrospective Study]) study III (2016-2020). SCI index was calculated as platelet count × fibrinogen/white blood cell count on admission. By adding SCI index, a nomogram was developed and evaluated for 90-day mortality prediction with conventional predictors via the Cox model with 10-fold cross-validation. RESULTS Patients were stratified with low SCI (<40), middle SCI (40-100), or high SCI (>100). The 90-day survival rates increased with SCI index (low 86.9%; [95% CI: 84.9%-89.0%], middle 92.7% [95% CI: 90.9%-94.9%], and high 96.4% [95% CI: 94.2%-98.6%]; log-rank P < 0.001). SCI index is independently associated with 90-day mortality (adjusted hazard ratio: 0.549; 95% CI: 0.424-0.710; P < 0.001). The addition of SCI index provided significantly incremental prognostic value to base model including age, serum creatinine, DeBakey class, and location of intimal entry (area under the curve: 0.677; 95% CI: 0.641-0.716 vs 0.724; 95% CI: 0.685-0.760; P = 0.002), which was confirmed by net reclassification improvement index (0.158; 95% CI: 0.065-0.235; P < 0.001) and integrated discrimination improvement index (0.070; 95% CI: 0.007-0.036; P < 0.001). CONCLUSIONS SCI index is easily obtainable, performs moderately well as a predictor of short-term mortality in ATAAD patients, and may be useful for risk stratification in emergency settings. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [Multicenter Retrospective Study] III NCT04918108).
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Affiliation(s)
- Hong Liu
- Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Si-chong Qian
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yong-feng Shao
- Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hai-yang Li
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hong-jia Zhang
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
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Chen Y, Xu X, Chen Z, Huang B, Wang X, Fan X. DNA methylation alternation in Stanford- A acute aortic dissection. BMC Cardiovasc Disord 2022; 22:455. [PMID: 36309656 PMCID: PMC9618190 DOI: 10.1186/s12872-022-02882-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 09/26/2022] [Indexed: 11/29/2022] Open
Abstract
Background Acute aortic dissection (AAD) is a life-threatening cardiovascular disease. Recent studies have shown that DNA methylation may be associated with the pathological mechanism of AAD, but the panorama of DNA methylation needs to be explored. Methods DNA methylation patterns were screened using Infinium Human Methylation 450 K BeadChip in the aortic tissues from 4 patients with Stanford-A AAD and 4 controls. Gene enrichment was analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO). DNA methylation levels of candidate genes were determined by pyrosequencing in the replication cohort including 16 patients with AAD and 7 controls. Protein expression level of candidate gene was assessed by Western blot. Results A total of 589 differentially methylated positions including 315 hypomethylated and 274 hypermethylated positions were found in AAD group. KEGG analysis demonstrated that differentially methylated position-associated genes were enriched in MAPK signaling pathway, TNF signaling pathway and apoptosis pathway, et al. GO analysis demonstrated that differentially methylated position-associated genes were enriched in protein binding, angiogenesis and heart development et al. The differential DNA methylation in five key genes, including Fas, ANGPT2, DUSP6, FARP1 and CARD6, was authenticated in the independent replication cohort. The protein expression level of the Fas was increased by 1.78 times, indicating the possible role of DNA methylation in regulation of gene expression. Conclusion DNA methylation was markedly changed in the aortic tissues of Stanford-A AAD and associated with gene dysregulation, involved in AAD progression. Supplementary Information The online version contains supplementary material available at10.1186/s12872-022-02882-5.
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Li Z, Zhang H, Baraghtha S, Mu J, Matniyaz Y, Jiang X, Wang K, Wang D, Xue YX. Short- and Mid-Term Survival Prediction in Patients with Acute Type A Aortic Dissection Undergoing Surgical Repair: Based on the Systemic Immune-Inflammation Index. J Inflamm Res 2022; 15:5785-5799. [PMID: 36238764 PMCID: PMC9553311 DOI: 10.2147/jir.s382573] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/27/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose The postoperative survival of patients with acute type A aortic dissection (aTAAD) remains unsatisfactory. The current study developed an easy-to-use survival prediction model and calculator. Methods A total of 496 patients with aTAAD undergoing surgical repair were included in this study. The systemic immune-inflammation index (SII) and other clinical features were collected and subjected to logistic and Cox regression analyses. The survival prediction model was based on Cox regression analyses and exhibited as a nomogram. For convenience of use, the nomogram was further developed into calculator software. Results We demonstrated that a higher preoperative SII was associated with in-hospital death (OR: 4.116, p < 0.001) and a higher postoperative overall survival rate (HR: 2.467, p < 0.001) in aTAAD patients undergoing surgical repair. A survival prediction model and calculator based on SII and four other clinical features were developed. The overall C-index of the model was 0.743. The areas under the curves (AUCs) of the 1- and 3-month and 1- and 3-year survival probabilities were 0.73, 0.71, 0.71 and 0.72, respectively. The model also showed good calibration and clinical utility. Conclusion Preoperative SII is significantly associated with postoperative survival. Based on SII and other clinical features, we created the first easy-to-use prediction model and calculator for predicting the postoperative survival rate in aTAAD patients, which showed good prediction performance.
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Affiliation(s)
- Zeshi Li
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - He Zhang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Sulaiman Baraghtha
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China,International School, University of Mannheim, Mannheim, Baden-Württemberg, Federal Republic of Germany
| | - Jiabao Mu
- School of Data Science, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China
| | - Yusanjan Matniyaz
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China
| | - Xinyi Jiang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China
| | - Kuo Wang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of XuZhou Medical University, Nanjing, People’s Republic of China
| | - Dongjin Wang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Nanjing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China,Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of XuZhou Medical University, Nanjing, People’s Republic of China
| | - Yun Xing Xue
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China,Correspondence: Yun Xing Xue; Dongjin Wang, Email ;
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Sawada H, Ohno-Urabe S, Ye D, Franklin MK, Moorleghen JJ, Howatt DA, Mullick AE, Daugherty A, Lu HS. Inhibition of the Renin-Angiotensin System Fails to Suppress β-Aminopropionitrile-Induced Thoracic Aortopathy in Mice-Brief Report. Arterioscler Thromb Vasc Biol 2022; 42:1254-1261. [PMID: 36004642 PMCID: PMC9492637 DOI: 10.1161/atvbaha.122.317712] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cross-linking of lysine residues in elastic and collagen fibers is a vital process in aortic development. Inhibition of lysyl oxidase by BAPN (β-aminopropionitrile) leads to thoracic aortopathies in mice. Although the renin-angiotensin system contributes to several types of thoracic aortopathies, it remains unclear whether inhibition of the renin-angiotensin system protects against aortopathy caused by the impairment of elastic fiber/collagen crosslinking. METHODS BAPN (0.5% wt/vol) was started in drinking water to induce aortopathies in male C57BL/6J mice at 4 weeks of age for 4 weeks. Five approaches were used to investigate the impact of the renin-angiotensin system. Bulk RNA sequencing was performed to explore potential molecular mechanisms of BAPN-induced thoracic aortopathies. RESULTS Losartan increased plasma renin concentrations significantly, compared with vehicle-infused mice, indicating effective angiotensin II type 1 receptor inhibition. However, losartan did not suppress BAPN-induced aortic rupture and dilatation. Since losartan is a surmountable inhibitor of the renin-angiotensin system, irbesartan, an insurmountable inhibitor, was also tested. Although increased plasma renin concentrations indicated effective inhibition, irbesartan did not ameliorate aortic rupture and dilatation in BAPN-administered mice. Thus, BAPN-induced thoracic aortopathies were refractory to angiotensin II type 1 receptor blockade. Next, we inhibited angiotensin II production by pharmacological or genetic depletion of AGT (angiotensinogen), the unique precursor of angiotensin II. However, neither suppressed BAPN-induced thoracic aortic rupture and dilatation. Aortic RNA sequencing revealed molecular changes during BAPN administration that were distinct from other types of aortopathies in which angiotensin II type 1 receptor inhibition protects against aneurysm formation. CONCLUSIONS Inhibition of either angiotensin II action or production of the renin-angiotensin system does not attenuate BAPN-induced thoracic aortopathies in mice.
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Affiliation(s)
- Hisashi Sawada
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
- Department of Physiology, University of Kentucky, Lexington, KY
| | - Satoko Ohno-Urabe
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
| | - Dien Ye
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
| | - Michael K. Franklin
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
| | - Jessica J. Moorleghen
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
| | - Deborah A. Howatt
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
| | | | - Alan Daugherty
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
- Department of Physiology, University of Kentucky, Lexington, KY
| | - Hong S. Lu
- Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY
- Saha Aortic Center, University of Kentucky, Lexington, KY
- Department of Physiology, University of Kentucky, Lexington, KY
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Potential of Disease-Modifying Anti-Rheumatic Drugs to Limit Abdominal Aortic Aneurysm Growth. Biomedicines 2022; 10:biomedicines10102409. [PMID: 36289670 PMCID: PMC9598733 DOI: 10.3390/biomedicines10102409] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/28/2022] [Accepted: 09/20/2022] [Indexed: 11/30/2022] Open
Abstract
Inflammation is strongly implicated in the pathogenesis of abdominal aortic aneurysms (AAA). This review examined the potential role of biologic disease-modifying anti-rheumatic drugs (bDMARDs) as repurposed drugs for treating AAA. Published evidence from clinical and preclinical studies was examined. Findings from animal models suggested that a deficiency or inhibition of tumour necrosis factor-α (TNF-α) (standard mean difference (SMD): −8.37, 95% confidence interval (CI): −9.92, −6.82), interleukin (IL)-6 (SMD: −1.44, 95% CI: −2.85, −0.04) and IL-17 (SMD: −3.36, 95% CI: −4.21, −2.50) led to a significantly smaller AAA diameter compared to controls. Human AAA tissue samples had significantly increased TNF-α (SMD: 1.68, 95% CI: 0.87, 2.49), IL-1β (SMD: 1.93, 95% CI: 1.08, 2.79), IL-6 (SMD: 2.56, 95% CI: 1.79, 3.33) and IL-17 (SMD: 6.28, 95% CI: 3.57, 8.99) levels compared to non-AAA controls. In human serum, TNF-α (SMD: 1.11, 95% CI: 0.25, 1.97) and IL-6 (SMD: 1.42, 95% CI: 0.91, 1.92) levels were significantly elevated compared to non-AAA controls. These findings implicate TNF-α, IL-17 and IL-6 in AAA pathogenesis. Randomised controlled trials testing the value of bDMARDs in limiting AAA growth may be warranted.
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Qin X, Gao Y, Jiang Y, Zhu F, Xie W, Tang X, Xue Y, Wang D, Cao H. The role of peripheral blood eosinophil counts in acute Stanford type A aortic dissection patients. Front Surg 2022; 9:969995. [PMID: 36111225 PMCID: PMC9468214 DOI: 10.3389/fsurg.2022.969995] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/11/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundAcute Stanford-A aortic dissection (AAAD) is a devastating cardiovascular condition with high mortality, therefore identifying risk prognosis factors is vital for the risk stratification of patients with AAAD. Here, we investigated peripheral blood eosinophil (EOS) counts in patients with AAAD and their possible biological implications.MethodsWe performed a single center retrospective cohort study. From 2011 to 2021, a total of 1,190 patients underwent AAAD surgery. Patients were categorized first by death and then admission EOS counts (0.00 × 109/L or >0.00 × 109/L). Demographics, laboratory data, and outcomes were analyzed using standard statistical analyses. Ascending aorta specimens were used for western blotting and histological assessments.ResultsDeath group patients had lower EOS counts than the non-death group (P = 0.008). When patients were stratified using mean blood EOS counts: 681 patients had low (0.00 × 109/L) and 499 had high (>0.00 × 109/L) counts. Patients with low EOS counts at admission were more likely to have a higher mortality risk (P = 0.017) and longer treatment in the intensive care unit (ICU) days (P = 0.033) than patients with normal EOS counts. Also, the five blood coagulation items between both groups showed significantly different (P < 0.001). Hematoxylin & eosin-stained cross-sections of the ascending aorta false lumen showed that EOSs were readily observed in thrombi in the false lumen of the aorta.ConclusionsPeripheral blood EOS counts may be involved in thrombosis and could be an effective and efficient indicator for the diagnosis, evaluation, and prognosis monitoring of patients with AAAD.
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Affiliation(s)
- Xichun Qin
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Yaxuan Gao
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Yi Jiang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Feng Zhu
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Wei Xie
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Xinlong Tang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Yunxing Xue
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
| | - Dongjin Wang
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
- Correspondence: Hailong Cao Dongjin Wang
| | - Hailong Cao
- Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing, China
- Correspondence: Hailong Cao Dongjin Wang
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Jiang Y, Tang X, Wang Y, Chen W, Xue Y, Cao H, Zhang B, Pan J, Zhou Q, Wang D, Fan F. Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection. Metabolites 2022; 12:metabo12070587. [PMID: 35888709 PMCID: PMC9324768 DOI: 10.3390/metabo12070587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/13/2022] [Accepted: 06/20/2022] [Indexed: 12/08/2022] Open
Abstract
Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.
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Affiliation(s)
- Yi Jiang
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Xinlong Tang
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Yali Wang
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Wei Chen
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Yunxing Xue
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Hailong Cao
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Bomin Zhang
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Jun Pan
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Qing Zhou
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
| | - Dongjin Wang
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
- Correspondence: (D.W.); (F.F.)
| | - Fudong Fan
- Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China
- Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China
- Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China
- Correspondence: (D.W.); (F.F.)
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Pang J, Liu J, Liang W, Yang L, Wu L. High Neutrophil-to-Platelet Ratio Is Associated with Poor Survival in Patients with Acute Aortic Dissection. DISEASE MARKERS 2022; 2022:5402507. [PMID: 35774849 PMCID: PMC9239768 DOI: 10.1155/2022/5402507] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Acute aortic dissection (AAD), a serious and fatal cardiovascular disease, is characterized by inflammation that may further aggravate the condition. We evaluated the value of the neutrophil-to-platelet ratio (NPR) in the prognosis of AAD. METHODS We collected records of patients with AAD and clinical data from 2010 to 2020 and followed up on the relevant information for 136 months. The Kaplan-Meier (K-M) survival along with the univariate and multivariate Cox analyses was used to examine the prognostic value of NPR in AAD. In addition, nomograms were constructed by combining NPR, age, Stanford typing, and treatment methods. The accuracy of nomograms was evaluated using calibration plots, and the prediction efficiency of nomograms was evaluated by receiver operating characteristic curve analysis and decision curve analysis (DCA). RESULTS The K-M analysis showed that AAD patients with higher NPR exhibited worse prognosis. In addition, different Stanford typing and treatment methods produced varied prognosis results. Univariate and multivariate Cox analyses showed that NPR value, age, classification, and treatment were independent prognostic factors for the overall survival time of patients with AAD. Nomograms constructed by combining NPR, age, Stanford typing, and treatment methods showed good predictive efficacy, and the AUC values for 1-, 3-, and 5-year predicting were 0.82, 0.79, and 0.74, respectively. CONCLUSIONS Our results suggest that pretreatment NPR can be used as a potential prognostic marker of overall survival time in patients with AAD.
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Affiliation(s)
- Jungang Pang
- Department of Cardiology, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
| | - Jun Liu
- Medical Research Center and Clinical Laboratory Medicine, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
| | - Wantian Liang
- Department of Cardiology, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
| | - Lijun Yang
- Department of Cardiology, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
| | - Liangyin Wu
- Department of Cardiology, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
- Medical Research Center and Clinical Laboratory Medicine, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan 512025, China
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Li Z, Wang J, Yu Q, Shen R, Qin K, Zhang Y, Qiao Y, Chi Y. Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection. Front Genet 2022; 13:911750. [PMID: 35795203 PMCID: PMC9252449 DOI: 10.3389/fgene.2022.911750] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 05/27/2022] [Indexed: 12/04/2022] Open
Abstract
Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear. Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein–protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm. Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell–cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group. Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.
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Affiliation(s)
- Zhaoshui Li
- Qingdao Medical College, Qingdao University, Qingdao, China
- Cardiac Surgery Department, Qingdao Hiser Hospital Affiliated to Qingdao University, Qingdao, China
| | - Jumiao Wang
- Cardiac Surgical Care Unit Department, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China
| | - Qiao Yu
- Hematology Department, Qingdao Hiser Hospital Affiliated to Qingdao University, Qingdao, China
| | - Ruxin Shen
- Qingdao Medical College, Qingdao University, Qingdao, China
| | - Kun Qin
- Qingdao Medical College, Qingdao University, Qingdao, China
| | - Yu Zhang
- Qingdao Medical College, Qingdao University, Qingdao, China
| | - Youjin Qiao
- Cardiac Surgery Department, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China
| | - Yifan Chi
- Cardiac Surgery Department, Qingdao Hiser Hospital Affiliated to Qingdao University, Qingdao, China
- *Correspondence: Yifan Chi,
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Chiba Y, Tashima Y, Ohama S, Teruaki K, Nakamura N, Sano T, Adachi K, Kimura N, Sanui M, Yamaguchi A. Effect of nadir hematocrit during cardiopulmonary bypass on the early outcomes after surgical repair of acute type A aortic dissection. J Card Surg 2022; 37:2338-2347. [PMID: 35545926 DOI: 10.1111/jocs.16590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/05/2022] [Accepted: 04/17/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Although hemodilution during hypothermic cardiopulmonary bypass (CPB) had been thought to improve microcirculation and reduce blood viscosity, there has been no report investigating the effect of low nadir hematocrit (Hct) values caused by severe hemodilution on the surgical outcomes of patients with acute type A aortic dissection (ATAAD). METHODS We retrospectively reviewed 112 consecutive patients who emergently underwent emergency surgical repair of ATAAD at our institution. The patients were classified into the high Hct (nadir Hct ≥ 21% during CPB; n = 51) and low Hct (nadir Hct < 21% during CPB; n = 61) groups. After propensity score matching of preoperative characteristics, surgical outcomes were compared between the groups. RESULTS Although there was no difference in the surgical procedure, longer CPB time and more blood transfusion during surgery were needed in the low Hct group than in the high Hct group. After surgery, estimated glomerular filtration rate was significantly lower (p = .015), lactaic acid was higher (p = .045), and intubation time was longer (p = .018) in the low Hct group than in the high Hct group, although there was no difference in hospital mortality between the groups. The AUC of the nadir Hct during CPB as a prognostic indicator of prolonged postoperative ventilator support was 0.8, with the highest accuracy at 16.7% (sensitivity 88%, specificity 76.9%). In all cohorts, female sex was an independent risk factor for a lower nadir Hct value of <21% during CPB. CONCLUSION A lower nadir Hct value of <21% during CPB may be associated with postoperative renal dysfunction and prolonged ventilator support in patients with ATAAD.
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Affiliation(s)
- Yoshihiko Chiba
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Yasushi Tashima
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Shinnosuke Ohama
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Kano Teruaki
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Noriyuki Nakamura
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Taichi Sano
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Koichi Adachi
- Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Kanagawa, Japan.,Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Naoyuki Kimura
- Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Masamitsu Sanui
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Atsushi Yamaguchi
- Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan
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Yin ZQ, Han H, Yan X, Zheng QJ. Research progress on the pathogenesis of aortic dissection. Curr Probl Cardiol 2022:101249. [PMID: 35568084 DOI: 10.1016/j.cpcardiol.2022.101249] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 05/06/2022] [Indexed: 12/20/2022]
Abstract
Aortic dissection (AD) is a critical cardiovascular disease due to the separation of media and adventitia caused by the rupture of vascular wall intima. The disease has a high mortality rate of about 1% to 3% for each additional hour, since the adventitia of the aorta can rupture and bleed to death at any time. Although great progress has been made in clinical treatment of aortic dissection, and the mortality rate has been significantly reduced, the pathogenesis is still not very clear. At present, related studies have confirmed that inflammation of aortic wall promotes the occurrence and development of AD. Although the mechanism of aortic dissection is more complicated, some studies have shown that the infiltration of monocytes/macrophages into the aortic wall is the main pathogenic mechanism of the disease. This review introduces the latest research results on the mechanism of macrophage infiltration and plasticity in aortic dissection.
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Affiliation(s)
- Zhi-Qiang Yin
- Department of Cardiovascular Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University); The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shanxi, China
| | - Hua Han
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shanxi, China
| | - Xianchun Yan
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shanxi, China
| | - Qi-Jun Zheng
- Department of Cardiovascular Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University); The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China.
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Different gene co-expression patterns of aortic intima-media and adventitia in thoracic aortic aneurysm. Gene 2022; 819:146233. [PMID: 35121027 DOI: 10.1016/j.gene.2022.146233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 01/04/2022] [Accepted: 01/18/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Due to permanent aortic dilation, thoracic aortic aneurysm (TAA) is a life-threatening disease. Once ruptured, TAA has a high lethality and disability rate. Although studies have focused on transcriptomic alterations in TAA, more detailed analysis is still lacking, especially the different aortic intima-media and adventitia roles. This study aimed to identify the different co-expression patterns between the aortic intima-media and the adventitia underlying the aortic dilation. METHODS We analyzed the gene expression profiles obtained from Gene Expression Omnibus (GEO, GSE26155) database. With a false discovery rate (FDR) < 0.05 and |log2FC| ≥ 1, 56 and 33 differential genes in the intima-media and adventitia, respectively, between the non-dilated and dilated status. Gene ontology (GO) and gene set enrichment analysis revealed that degranulation and activation of neutrophils play an essential role in the intima-media of dilated aortas. Through weighted gene co-expression network analysis (WGCNA), we identified essential co-expressed modules and hub genes to explore the biological functions of the dysregulated genes. RESULTS Functional pathway analysis suggested that lipid metabolism, C-C motif chemokine pathways were significantly enriched in the adventitia, whereas ribosome proteins and related mRNA translation pathways were closely related to intima and media. Furthermore, the ssGSEA analysis indicated that macrophages, helper T cells, and neutrophils were higher in the intima-media of the dilated thoracic aorta. Finally, we validated the critical findings of the study with the murine model of TAA. CONCLUSION This study identified and verified hub genes and pathways in aortic intima-media and adventitia prominently associated with aortic dilation, providing practical understanding in the perspective of searching for new molecular targets.
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Role of Necroptosis and Immune Infiltration in Human Stanford Type A Aortic Dissection: Novel Insights from Bioinformatics Analyses. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:6184802. [PMID: 35480868 PMCID: PMC9036163 DOI: 10.1155/2022/6184802] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 02/28/2022] [Accepted: 03/18/2022] [Indexed: 12/21/2022]
Abstract
Background Stanford type A aortic dissection (TAAD) is one of the most life-threatening cardiovascular emergencies with high mortality and morbidity, and necroptosis is a newly identified type of programmed cell death and contributes to the pathogenesis of various cardiovascular diseases. However, the role of necroptosis in TAAD has not been elucidated. This study was aimed at determining the role of necroptosis in TAAD using bioinformatics analyses. Methods The RNA sequencing dataset GSE153434 and the microarray dataset GSE52093 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes of necroptosis (NRDEGs) were identified based on differentially expressed genes (DEGs) and necroptosis gene set. Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks and identify the key functional modules of NRDEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of NRDEGs were also performed. Additionally, Spearman correlations were used to construct the necroptosis-related transcription factor-target genes regulatory network, immune infiltration patterns were analyzed using the ImmuCellAI algorithm, and the correlation between immune cell-type abundance and NRDEGs expression was investigated. The expression levels of NRDEGs and immune infiltration were additionally verified in the GSE52093 dataset. Results We found that the necroptosis pathway was considerably enriched and activated in TAAD samples. Overall, 25 NRDEGs were identified including MLKL, RIPK1, and FADD, and among them, 18 were verified in the validation set. Moreover, GO and KEGG enrichment analyses found that NRDEGs were primarily involved in the tumor necrosis factor signaling pathway, nucleotide-binding oligomerization domain-like receptor signaling pathway, and interleukin-17 signaling pathway. The imbalance of Th17/Treg cells was identified in the TAAD samples. Furthermore, correlation analysis indicated that expression of NRDEGs was positively associated with proinflammatory immune-cell infiltrations and negatively associated with anti-inflammatory or regulatory immune-cell infiltrations. Conclusions The present findings suggest that necroptosis phenomenon exists in TAAD and correlates with immune cell infiltration, which indicate necroptosis may promote the development of TAAD through activating immune infiltration and immune response. This study paves a new road to future investigation of the pathogenic mechanisms and therapeutic strategies for TAAD.
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Hu YY, Cheng XM, Wu N, Tao Y, Wang XN. Non-coding RNAs Regulate the Pathogenesis of Aortic Dissection. Front Cardiovasc Med 2022; 9:890607. [PMID: 35498004 PMCID: PMC9051029 DOI: 10.3389/fcvm.2022.890607] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 03/29/2022] [Indexed: 12/14/2022] Open
Abstract
Aortic dissection (AD) is a fatal cardiovascular disease. It is caused by a rupture of the aortic intima or bleeding of the aortic wall that leads to the separation of different aortic wall layers. Patients with untreated AD have a mortality rate of 1–2% per hour after symptom onset. Therefore, effective biomarkers and therapeutic targets are needed to reduce AD-associated mortality. With the development of molecular technology, researchers have begun to explore the pathogenesis of AD at gene and protein levels, and have made some progress, but the pathogenesis of AD remains unclear. Non-coding RNAs, such as microRNAs, lncRNAs, and circRNAs, have been identified as basic regulators of gene expression and are found to play a key role in the pathogenesis of AD. Thus, providing a theoretical basis for developing these non-coding RNAs as clinical biomarkers and new therapeutic targets for AD in the future. Previous studies on the pathogenesis of AD focused on miRNAs, but recently, there have been an increasing number of studies that explore the role of lncRNAs, and circRNAs in AD. This review summarizes the existing knowledge on the roles of various non-coding RNAs in the pathogenesis of AD, discusses their potential role as clinical biomarkers and therapeutic targets, states the limitations of existing evidence, and recommends future avenues of research on the pathogenesis of AD.
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Qi F, Liu Y, Zhang K, Zhang Y, Xu K, Zhou M, Zhao H, Zhu S, Chen J, Li P, Du J. Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection. Front Cardiovasc Med 2022; 9:871486. [PMID: 35463768 PMCID: PMC9019136 DOI: 10.3389/fcvm.2022.871486] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 02/25/2022] [Indexed: 11/13/2022] Open
Abstract
Thoracic aortic aneurysm and dissection (TAAD) is a lethal cardiovascular condition without effective pharmaceutical therapy. Identifying novel drugs that target the key pathogenetic components is an urgent need. Bioinformatics analysis of pathological studies indicated “extracellular matrix organization” as the most significant functional pathway related to TAAD, in which matrix metallopeptidase (MMP) 2 and MMP9 ranked above other proteases. MMP1-14 were designated as the prototype molecules for docking against PubChem Compound Database using Surflex-Dock, and nine natural compounds were identified. Using a generic MMP activity assay and an aminopropionitrile (BAPN)-induced TAAD mouse model, we identified crocin as an effective MMP inhibitor, suppressing the occurrence and rupture of TAAD. Biolayer interferometry and AI/bioinformatics analyses indicated that crocin may inhibit MMP2 activity by direct binding. Possible binding sites were investigated. Overall, the integration of artificial intelligence and functional experiments identified crocin as an MMP inhibitor with strong therapeutic potential.
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Affiliation(s)
- Feiran Qi
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Yan Liu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Kunlin Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Yanzhenzi Zhang
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Ke Xu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Mei Zhou
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Huinan Zhao
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Shuolin Zhu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
| | - Jianxin Chen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Jianxin Chen
| | - Ping Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Ping Li
| | - Jie Du
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Jie Du
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Liu Y, Zou L, Tang H, Li J, Liu H, Jiang X, Jiang B, Dong Z, Fu W. Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity. Front Cardiovasc Med 2022; 9:791875. [PMID: 35433892 PMCID: PMC9008490 DOI: 10.3389/fcvm.2022.791875] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 03/14/2022] [Indexed: 11/25/2022] Open
Abstract
Background Inflammation plays an important role in the progression of sporadic aortic dissection (AD). Immune cells, especially macrophages, infiltrate the aorta and secrete inflammatory cytokines and matrix metalloproteinases to cause degradation of the extracellular matrix, thereby contributing to the pathogenesis of AD. However, the cellular heterogeneity within these immune cells has not been fully characterized. Methods We used single-cell RNA sequencing to profile the transcriptomes of all immune cells in AD tissue and normal aorta. Using magnetic-activated cell sorting gating on CD45, we obtained a higher resolution identification of the immune cell subsets in the aorta. Results We observed significant differences in the proportion of major immune cell subpopulations between AD and normal aorta tissues. Macrophages accounted for a higher percentage in the normal aorta, while the proportions of T cells, B cells and natural killer (NK) cells were all increased in AD tissues. Macrophage clusters that expanded in AD tissues originated primarily from circulating monocytes and expressed genes encoding proinflammatory cytokines and molecules involved in tissue repair. T and NK cells in AD tissues exhibited enhanced cytotoxic properties. A cluster of CD4+ T cells that had expanded in AD tissues was Th17-like and might contribute to the pathogenesis of AD. Cell–cell interaction analysis highlighted the increased communication between macrophages and T cells, which primarily regulated the costimulation of T cells. Conclusions Our study provides a comprehensive characterization of immune cells in the dissected aorta with an emphasis on the role of macrophages and T cells. The information from our study improves our understanding of immune mechanisms in AD formation and helps to identify additional useful targets for early diagnosis or therapy of AD.
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Affiliation(s)
- Yifan Liu
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Lingwei Zou
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Hanfei Tang
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Jie Li
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Hao Liu
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Xiaolang Jiang
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
| | - Baohong Jiang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- *Correspondence: Weiguo Fu
| | - Zhihui Dong
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
- Zhihui Dong
| | - Weiguo Fu
- Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- National Clinical Research Center for Interventional Medicine, Shanghai, China
- Baohong Jiang
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Mendes R, Nascimento CRD, Fonseca JHDAPD, Tenório PP. Acute thoracic aorta dissection: unraveling the pathophysiology of a silent killer. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2022; 68:268-272. [PMID: 35239894 DOI: 10.1590/1806-9282.20210939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/24/2021] [Indexed: 11/22/2022]
Affiliation(s)
- Rodrigo Mendes
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Campus São Paulo - São Paulo (SP), Brazil
| | | | | | - Pedro Pereira Tenório
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Campus São Paulo - São Paulo (SP), Brazil.,Universidade Federal do Vale do São Francisco, Colegiado de Medicina, Campus Paulo Afonso - Paulo Afonso (BA), Brazil
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Biomechanics in ascending aortic aneurysms correlate with tissue composition and strength. JTCVS OPEN 2022; 9:1-10. [PMID: 36003475 PMCID: PMC9390473 DOI: 10.1016/j.xjon.2021.12.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 12/03/2021] [Indexed: 12/12/2022]
Abstract
Objective This study correlates low strain tangential modulus (LTM) and transition zone onset (TZo) stress, biomechanical parameters that occur within the physiological range of stress seen in vivo, with tissue strength and histopathologic changes in aneurysmal ascending aortic tissue. Method Ascending aortic aneurysm tissue samples were collected from 41 patients undergoing elective resection. Samples were subjected to planar biaxial testing to quantify LTM and TZo. These were then correlated with strength assessed from uniaxial testing and with histopathologic quantification of pathologic derangements in elastin, collagen, and proteoglycan (PG). Results Decreased LTM and TZo were correlated with reduced strength (P < .05), PG content (P < .05), and elastin content (P < .05). Reduced TZo also was correlated with increased elastin fragmentation (P < .05). Conclusions LTM and TZo are correlated with common biomechanical and histopathologic alterations in ascending aortic aneurysm tissue that are thought to relate to the risk of acute aortic syndromes. LTM and TZo are measured under conditions approximating in vivo physiology and have the potential to be obtained noninvasively using medical imaging techniques. Therefore, they represent parameters that warrant future study as potential contributors to our growing knowledge of pathophysiology, disease progression, and risk stratification of aortic disease.
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Xu H, Li Y, Wang H, Yuan Y, Chen D, Sun Y, Xu Z. Systemic immune-inflammation index predicted short-term outcomes in ATAD patients undergoing surgery. J Card Surg 2022; 37:969-975. [PMID: 35141947 DOI: 10.1111/jocs.16300] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/12/2021] [Accepted: 01/05/2022] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Systemic immune-inflammation index (SII) is a biomarker that reflect systemic inflammation. We aimed to assess the value of SII in prediction of short-term outcomes in acute type A aortic dissection (ATAD) patients undergoing surgery. METHOD All patients underwent surgery for ATAD at our institution from 2018 to 2020 (n = 324) were retrospectively reviewed and divided into low SII (<1582.6 × 109 /L) and high SII (≥1582.6 × 109 /L) group according to optimal cut-off values defined by receiver operating characteristic curve. Cox regression and Kaplan-Meier analyses were performed to illustrate the correlation between SII and postoperative short-outcomes, including 30-day mortality and main complications after surgery. RESULTS In total, 48 (14.8%) patients died in 30 days after ATAD surgery. And multivariable Cox analysis demonstrated that high preoperative SII was closely related with 30-day mortality (hazard ratio: 3.532, 95% confidence interval: 1.719-7.255, p = .001). Furthermore, Kaplan-Meier analysis illustrated that the short-term mortality rate increased significantly in high SII group (p < .001). In addition, the incidence of main postoperative complications including major adverse cardiovascular events (p = .001) and multiorgan failure (p = .002) were higher in high SII group. However, the length of intensive unit stay (p = .909) and hospital stay (p = .836) presented no difference in two groups. CONCLUSION The study indicated that SII was an available biomarker to predict postoperative short-term prognosis, but not length of stay in intensive care unit and hospital in ATAD patients. And SII may be applied to risk stratification and patient selection in ATAD patients before surgery.
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Affiliation(s)
- Hongjie Xu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
| | - Yang Li
- Department of Thoracic Surgery, 3rd Medical Center of PLA General Hospital, Beijing, China
| | - He Wang
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
| | - Ye Yuan
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
| | - Di Chen
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
| | - Yangyong Sun
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
| | - Zhiyun Xu
- Department of Cardiovascular Surgery, Changhai Hospital, The Naval Medical University, Shanghai, China
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Crucial Genes in Aortic Dissection Identified by Weighted Gene Coexpression Network Analysis. J Immunol Res 2022; 2022:7585149. [PMID: 35178459 PMCID: PMC8844153 DOI: 10.1155/2022/7585149] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 12/07/2021] [Accepted: 12/31/2021] [Indexed: 01/01/2023] Open
Abstract
Background Aortic dissection (AD) is a lethal vascular disease with high mortality and morbidity. Though AD clinical pathology is well understood, its molecular mechanisms remain unclear. Specifically, gene expression profiling helps illustrate the potential mechanism of aortic dissection in terms of gene regulation and its modification by risk factors. This study was aimed at identifying the genes and molecular mechanisms in aortic dissection through bioinformatics analysis. Method Nine patients with AD and 10 healthy controls were enrolled. The gene expression in peripheral mononuclear cells was profiled through next-generation RNA sequencing. Analyses including differential expressed gene (DEG) via DEGseq, weighted gene coexpression network (WGCNA), and VisANT were performed to identify crucial genes associated with AD. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was also utilized to analyze Gene Ontology (GO). Results DEG analysis revealed that 1,113 genes were associated with AD. Of these, 812 genes were markedly reduced, whereas 301 genes were highly expressed, in AD patients. DEGs were rich in certain categories such as MHC class II receptor activity, MHC class II protein complex, and immune response genes. Gene coexpression networks via WGCNA identified 3 gene hub modules, with one positively and 2 negatively correlated with AD, respectively. Specifically, module 37 was the most strongly positively correlated with AD with a correlation coefficient of 0.72. Within module 37, five hub genes (AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D) displayed high connectivity and may have clinical significance in the pathogenesis of AD. Conclusion Our analysis provides the possible association of specific genes and gene modules for the involvement of the immune system in aortic dissection. AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D in module M37 were highly connected and strongly linked with AD, suggesting that these genes may help understand the pathogenesis of aortic dissection.
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