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Gouaref I, Otmane A, Makrelouf M, Abderrhmane SA, Haddam AEM, Koceir EA. Crucial Interactions between Altered Plasma Trace Elements and Fatty Acids Unbalance Ratio to Management of Systemic Arterial Hypertension in Diabetic Patients: Focus on Endothelial Dysfunction. Int J Mol Sci 2024; 25:9288. [PMID: 39273236 PMCID: PMC11395650 DOI: 10.3390/ijms25179288] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
The coexistence of SAH with T2DM is a common comorbidity. In this study, we investigated the link between altered plasma antioxidant trace elements (ATE: manganese, selenium, zinc, and copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile, which is modified during SAH-T2DM association compared to the healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of total SFA, palmitic acid, arachidonic acid, and PUFA ω6/PUFA ω3; drop in tandem of PUFA/SFA and EPA + DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA rise, concurrent drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitant enhancement of Cu, Mn, and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitant rise of ApoB100/ApoA1, Ox-LDL, tHcy, and Lp(a)), and inflammation (higher of Hs-CRP, fibrinogen and ferritin). Our study opens to new therapeutic targets and to better dietary management, such as to establishing dietary ATE and PUFA ω6/PUFA ω3 or PUFA/SFA reference values for atherosclerotic risk prevention in hypertensive/diabetic patients.
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Affiliation(s)
- Ines Gouaref
- Bioenergetics and Intermediary Metabolism Team, Laboratory of Biology and Organism Physiology, Biological Sciences Faculty, Nutrition and Pathologies Post Graduate School, Houari Boumediene University of Sciences and Technology (USTHB), Bab Ezzouar, Algiers 16123, Algeria
- Tamayouz Laboratory, Centre de Recherche en Biotechnologie (CRBT), Ali Mendjli Nouvelle Ville UV 03 BP E73, Constantine 25000, Algeria
| | - Amel Otmane
- Biochemistry and Genetics Laboratory, University Hospital Center, Mohamed Lamine Debaghine, Bab El Oued, Algiers 16000, Algeria
| | - Mohamed Makrelouf
- Biochemistry and Genetics Laboratory, University Hospital Center, Mohamed Lamine Debaghine, Bab El Oued, Algiers 16000, Algeria
| | - Samir Ait Abderrhmane
- Diabetology Unit, University Hospital Center, Mohamed Seghir Nekkache (ex. HCA de Aïn Naâdja), Algiers 16208, Algeria
| | - Ali El Mahdi Haddam
- Diabetology Unit, University Hospital Center, Mohamed Lamine Debaghine, Algiers I-University, Bab El Oued, Algiers 16000, Algeria
| | - Elhadj-Ahmed Koceir
- Bioenergetics and Intermediary Metabolism Team, Laboratory of Biology and Organism Physiology, Biological Sciences Faculty, Nutrition and Pathologies Post Graduate School, Houari Boumediene University of Sciences and Technology (USTHB), Bab Ezzouar, Algiers 16123, Algeria
- Tamayouz Laboratory, Centre de Recherche en Biotechnologie (CRBT), Ali Mendjli Nouvelle Ville UV 03 BP E73, Constantine 25000, Algeria
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Zhao X, Gao C, Chen H, Chen X, Liu T, Gu D. C-Reactive Protein: An Important Inflammatory Marker of Coronary Atherosclerotic Disease. Angiology 2024:33197241273360. [PMID: 39126663 DOI: 10.1177/00033197241273360] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2024]
Abstract
Cardiovascular disease (CVD) is the most common cause of death worldwide, with coronary atherosclerotic heart disease (CHD) accounting for the majority of events. Evidence demonstrates that inflammation plays a vital role in the development of CHD. The association between C-reactive protein (CRP), a representative inflammatory biomarker, and atherosclerosis (AS), CHD, and inflammation has attracted attention. Therefore, we conducted an extensive search on PubMed using the aforementioned terms as search criteria and identified a total of 1246 articles published from January 2000 to April 2024. Both review and research-based articles consistently indicate CRP as a risk enhancer for CVD, contributing to the refinement of risk stratification and early identification of apparently healthy at-risk populations. Additionally, CRP reflects disease progression and predicts the prognosis of recurrent cardiovascular events. Anti-inflammatory therapeutic strategies targeting CRP also provide new treatment options for patients. This review focuses on the link between CRP and CHD, highlighting how CRP is involved in the pathological progression of AS and its potential value for clinical applications.
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Affiliation(s)
- Xiaona Zhao
- Guangxi University of Chinese Medicine, Nanning, China
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Cheng Gao
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Hongfang Chen
- School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Guangdong, China
| | - Xi Chen
- Medical Department, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Tonggong Liu
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
| | - Dayong Gu
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China
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Zhao H, Wang S, Han Y, Yao M, Zhang Y, Zeng X. Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018. Eur J Nutr 2024; 63:1705-1718. [PMID: 38703226 DOI: 10.1007/s00394-024-03367-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 03/04/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. METHODS We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. RESULTS A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. CONCLUSION This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.
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Affiliation(s)
- He Zhao
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Shuolin Wang
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Yingdong Han
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Menghui Yao
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Yun Zhang
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China.
| | - Xuejun Zeng
- Department of Family Medicine, Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, 100730, China.
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Ma Y, Chen Y, Yang T, He X, Yang Y, Chen J, Han L. Blood biomarkers for post-stroke cognitive impairment: A systematic review and meta-analysis. J Stroke Cerebrovasc Dis 2024; 33:107632. [PMID: 38417566 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107632] [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: 10/15/2023] [Revised: 01/18/2024] [Accepted: 02/05/2024] [Indexed: 03/01/2024] Open
Abstract
BACKGROUND AND PURPOSE Post-stroke cognitive impairment (PSCI) is a frequent consequence of stroke, which affects the quality of life and prognosis of stroke survivors. Numerous studies have indicated that blood biomarkers may be the key determinants for predicting and diagnosing cognitive impairment, but the results remain varied. Therefore, this meta-analysis aims to summarize potential biomarkers associated with PSCI. METHODS PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched for studies exploring blood biomarkers associated with PSCI from inception to 15 April 2022. RESULTS 63 studies were selected from 4,047 references, which involves 95 blood biomarkers associated with the PSCI. We meta-analyzed 20 potential blood biomarker candidates, the results shown that the homocysteine (Hcy) (SMD = 0.35; 95 %CI: 0.20-0.49; P < 0.00001), c-reactive protein (CRP) (SMD = 0.49; 95 %CI: 0.20-0.78; P = 0.0008), uric acid (UA) (SMD = 0.41; 95 %CI: 0.06-0.76; P = 0.02), interleukin 6 (IL-6) (SMD = 0.92; 95 % CI: 0.27-1.57; P = 0.005), cystatin C (Cys-C) (SMD = 0.58; 95 %CI: 0.28-0.87; P = 0.0001), creatinine (SMD = 0.39; 95 %CI: 0.23-0.55; P < 0.00001) and tumor necrosis factor alpha (TNF-α) (SMD = 0.45; 95 %CI: 0.08-0.82; P = 0.02) levels were significantly higher in patients with PSCI than in the non-PSCI group. CONCLUSION Based on our findings, we recommend that paramedics focus on the blood biomarkers levels of Hcy, CRP, UA, IL-6, Cys-C, creatinine and TNF-α in conjunction with neuroimaging and neuropsychological assessment to assess the risk of PSCI, which may help with early detection and timely preventive measures. At the same time, other potential blood biomarkers should be further validated in future studies.
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Affiliation(s)
- Yuxia Ma
- The First School of Clinical Medicine, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China
| | - Yanru Chen
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China; National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China
| | - Tingting Yang
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China
| | - Xiang He
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China
| | - Yifang Yang
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China
| | - Junbo Chen
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China
| | - Lin Han
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu Province, 730000, PR China; Department of Nursing, Gansu Provincial Hospital, Lanzhou, Gansu Province, 730000, PR China.
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Zhang R, Wang Y, Liao L, Liao Y, Fang Y, Shen Y. The relationship between C-reactive protein/albumin ratio and mortality in hypertensive patients: A national cohort study. Nutr Metab Cardiovasc Dis 2024; 34:1601-1609. [PMID: 38519295 DOI: 10.1016/j.numecd.2024.02.011] [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: 12/11/2023] [Revised: 02/22/2024] [Accepted: 02/23/2024] [Indexed: 03/24/2024]
Abstract
BACKGROUND AND AIMS The impact of inflammation on the prognosis of hypertension has received some attention. The current study examined the association between C-reactive protein to albumin ratio (CAR), a novel indicator of inflammatory response, and mortality in individuals with hypertension. METHODS AND RESULTS A total of 9561 eligible individuals diagnosed with hypertension were included in the final analysis. CAR was calculated as ratio of C-reactive protein to serum albumin concentration. Patients were categorized into tertiles based on their baseline CAR levels. The Kaplan-Meier survival method was employed to compare the survival times of patients throughout the follow-up period. Multivariable analysis was conducted using the Cox proportional regression model. In the entire study population, 3262 (27%) experienced all-cause mortality. Patients in tertile 3 exhibited a higher risk of mortality (23% vs. 28% vs. 31%, P < 0.001) in comparison to those in the other tertiles. The findings from the multivariable Cox regression analysis demonstrated that when patients in tertile 1 were used as the reference group, the highest CAR tertile displayed a 60% increased risk of all-cause mortality (HR, 1.60 [95%CI, 1.23-2.09] P < 0.001). CONCLUSION Among hypertensive patients, elevated CAR was found to be associated with an increased risk of all-cause mortality. Therefore, CAR might be used for risk stratification within this population, facilitating the implementation of closer follow-up and the optimization of treatment strategies.
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Affiliation(s)
- Rongting Zhang
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Yani Wang
- Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, China
| | - Lihua Liao
- Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, China
| | - Ying Liao
- Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, China
| | - Yong Fang
- Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, China.
| | - Yunli Shen
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
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Acevedo-Villavicencio LN, López-Luna CE, Castillo-Cruz J, Gutiérrez-Rojas RA, Paredes-González IS, Villafaña S, Huang F, Vargas-De-León C, Romero-Nava R, Aguayo-Cerón KA. Modulator Effect of AT1 Receptor Knockdown on THP-1 Macrophage Proinflammatory Activity. BIOLOGY 2024; 13:382. [PMID: 38927262 PMCID: PMC11200961 DOI: 10.3390/biology13060382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 05/09/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024]
Abstract
Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1β, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1β, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1β and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1β via NF-κB in macrophages and having high blood pressure decrease.
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Affiliation(s)
- Lourdes Nallely Acevedo-Villavicencio
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
| | - Carlos Enrique López-Luna
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
| | - Juan Castillo-Cruz
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
| | | | - Iris Selene Paredes-González
- Instituto de Investigaciones Biomédicas, Departamento de Inmunología, Universidad Autónoma de México, Ciudad de México 70228, Mexico;
| | - Santiago Villafaña
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
| | - Fengyang Huang
- Laboratorio de Investigación en Obesidad y Asma, Hospital Infantil de México Federico Gómez, Ciudad de Mexico 06720, Mexico;
| | - Cruz Vargas-De-León
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
- División de Investigación, Hospital Juárez de Mexico, Mexico City 07760, Mexico
| | - Rodrigo Romero-Nava
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
| | - Karla Aidee Aguayo-Cerón
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Ciudad de México 11340, Mexico; (L.N.A.-V.); (C.E.L.-L.); (J.C.-C.); (S.V.); (C.V.-D.-L.)
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Marrone G, Cornali K, Di Lauro M, Ceravolo MJ, Di Marco L, Manca di Villahermosa S, Mitterhofer AP, Noce A. Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients. Biomedicines 2024; 12:1085. [PMID: 38791047 PMCID: PMC11117580 DOI: 10.3390/biomedicines12051085] [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: 04/08/2024] [Revised: 05/02/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.
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Affiliation(s)
- Giulia Marrone
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Kevin Cornali
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Manuela Di Lauro
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Maria Josè Ceravolo
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Luca Di Marco
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Simone Manca di Villahermosa
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Anna Paola Mitterhofer
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Annalisa Noce
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
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Xu J, Wu X, Zhu H, Zhu Y, Du K, Deng X, Wang C. CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway. Med Oncol 2024; 41:72. [PMID: 38345752 DOI: 10.1007/s12032-024-02301-z] [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: 07/03/2023] [Accepted: 01/05/2024] [Indexed: 02/15/2024]
Abstract
Inflammation disrupts bone metabolism and leads to bone damage. C-reactive protein (CRP) is a typical inflammation marker. Although CRP measurement has been conducted for many decades, how osteoblastic differentiation influences molecular mechanisms remains largely unknown. The present study attempted to investigate the effects of CRP on primary cultured osteoblast precursor cells (OPCs) while elucidating the underlying molecular mechanisms. OPCs were isolated from suckling Sprague-Dawleyrats. Fewer OPCs were observed after recombinant C-reactive protein treatment. In a series of experiments, CRP inhibited OPC proliferation, osteoblastic differentiation, and the OPC gene expression of the hedgehog (Hh) signaling pathway. The inhibitory effect of CRP on OPC proliferation occurred via blockade of the G1-S transition of the cell cycle. In addition, the regulation effect of proto cilium on osteoblastic differentiation was analyzed using the bioinformatics p. This revealed the primary cilia activation of recombinant CRP effect on OPCs through in vitro experiments. A specific Sonic Hedgehog signaling agonist (SAG) rescued osteoblastic differentiation inhibited by recombinant CRP. Moreover, chloral hydrate, which removes primary cilia, inhibited the Suppressor of Fused (SUFU) formation and blocked Gli2 degradation. This counteracted osteogenesis inhibition caused by CRP. Therefore, these data depict that CRP can inhibit the proliferation and osteoblastic differentiation of OPCs. The underlying mechanism could be associated with primary cilia activation and Hh pathway repression.
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Affiliation(s)
- Jie Xu
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Xiangmei Wu
- Department of Physiology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Huifang Zhu
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yinghua Zhu
- Department of Pre-Hospital Emergency, Chongqing Emergency Medical Center, Central Hospital of Chongqing University, Chongqing, 400014, China
| | - Kailong Du
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Xiaoyan Deng
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Changdong Wang
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
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Otani T, Moriguchi-Goto S, Nishihira K, Oguri N, Shibata Y, Matsuura Y, Kodama T, Asada Y, Hatakeyama K, Yamashita A. Intralesional pentraxin 3 increases with atherosclerotic disease progression, but may protect from thrombosis: Friend or foe? Thromb Res 2024; 234:134-141. [PMID: 38218110 DOI: 10.1016/j.thromres.2024.01.004] [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: 06/20/2023] [Revised: 11/20/2023] [Accepted: 01/04/2024] [Indexed: 01/15/2024]
Abstract
AIM To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). MATERIALS AND METHODS PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. RESULTS Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry-positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry-positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. CONCLUSIONS PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects.
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Affiliation(s)
- Tomoyuki Otani
- Department of Pathology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan; Department of Pathology, Kindai University Faculty of Medicine, 377-2 Ono-higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Sayaka Moriguchi-Goto
- Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan
| | - Kensaku Nishihira
- Department of Cardiology, Miyazaki Medical Association Hospital, 1173 Arita, Miyazaki 880-2102, Japan
| | - Nobuyuki Oguri
- Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan
| | - Yoshisato Shibata
- Department of Cardiology, Miyazaki Medical Association Hospital, 1173 Arita, Miyazaki 880-2102, Japan
| | - Yunosuke Matsuura
- Division of Cardiovascular Medicine and Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan
| | - Tatsuhiko Kodama
- Department of Nuclear Receptor Medicine, Laboratories for Systems Biology and Medicine (LSBM) at the Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan
| | - Yujiro Asada
- Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan; Department of Pathology, Miyazaki Medical Association Hospital, 1173 Arita, Miyazaki 880-2102, Japan
| | - Kinta Hatakeyama
- Department of Pathology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan; Department of Diagnostic Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
| | - Atsushi Yamashita
- Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, Miyazaki 889-1692, Japan
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10
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Luo Q, Zhang Y, Yang X, Qin L, Wang H. Hypertension in connective tissue disease. J Hum Hypertens 2024; 38:19-28. [PMID: 35505225 DOI: 10.1038/s41371-022-00696-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 02/23/2022] [Accepted: 04/12/2022] [Indexed: 11/10/2022]
Abstract
It is well documented that connective tissue disease (CTD) is a type of autoimmune disease characterized by chronic inflammation, which can occur across various organ systems throughout the whole body. Although the clinical manifestations of CTD are different, studies have shown that different CTD diseases have similar pathogenesis, implying that different CTD diseases may have similar clinical outcomes. Recent population-based studies have demonstrated an increased risk of cardiovascular disease (CVD) in patients with CTD compared with the control group, which is partially attributed to traditional cardiovascular risk factors, such as hypertension (HT), and that controlling the patients' blood pressure (BP) still constitutes one of the most effective means to prevent CVD. Although many studies have shown that the prevalence of HT in patients with CTD is higher than that in the general population, there is a lack of adequate data on the possible pathogenesis of HT. Also, the factors that promote the rise of BP, especially the relationship between connective tissue disease- hypertension (CTD-HT) and traditional cardiovascular risk factors (aging, sex, race, dyslipidemia, diabetes mellitus, smoking, obesity, etc.), have not been fully confirmed. In this review, we explore the mechanisms that might lead to elevated BP in patients with CTD and the factors that contribute to elevated BP and the management of CTD-HT, and we focus on whether traditional cardiovascular risk factors, the disease, and the presence of related therapeutic drugs are associated with an increased risk of HT in patients with CTD.
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Affiliation(s)
- Qiang Luo
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Yiwen Zhang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Xiaoqian Yang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Li Qin
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Han Wang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China.
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11
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Ye M, Yu G, Han F, He H. Non-linear Association of CAR with all-Cause and Cardiovascular Mortality in Coronary Heart Disease: A Retrospective Cohort Study from NHANES. Clin Appl Thromb Hemost 2024; 30:10760296241271382. [PMID: 39149979 PMCID: PMC11329957 DOI: 10.1177/10760296241271382] [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: 04/27/2024] [Revised: 06/17/2024] [Accepted: 06/25/2024] [Indexed: 08/17/2024] Open
Abstract
OBJECTIVE To investigate the relationship between C-reactive protein and albumin ratios (CAR) and all-cause and cardiovascular disease(CVD)-specific mortality in individuals with coronary heart disease(CHD). METHODS The data from 1895 patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database from 1999-2010. We used weighted COX regression analyses to explore the association between CAR, all-cause, and CVD-specific mortality. Restricted cubic spline(RCS) regression models and threshold effects analysis were used to analyze nonlinear relationships. Subgroup analyses were also performed to explore these relationships further. RESULTS During a mean follow-up of 115.78 months, 61.48% of deaths occurred, and 21.85% were due to CVD. After adjusting for potential confounders, each 1-unit increase in CAR was associated with a 65% increase in all-cause mortality and a 67% increase in CVD-specific mortality. The RCS model revealed a non-linear association between CAR and the risk of all-cause mortality and CVD-specific mortality in CHD patients (all non-linear P < 0.001). Threshold effects analysis identified inflection points in regression models of all-cause mortality (0.04, P < 0.001) and CVD-specific mortality (0.05, P = 0.0024). The interaction tests found sex, smoking and diabetes influenced the association between CAR and all-cause mortality and sex, smoking and HF influenced its association with CVD-specific mortality (all P < 0.05). CONCLUSION There was a nonlinear association between CAR and all-cause mortality and CVD mortality in patients with CHD, with a higher hazard ratio before the inflection point. Sex, smoking, diabetes, and HF might have an effect on the associations between CAR and death risks.
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Affiliation(s)
- Ming Ye
- Department of Emergency Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Guangzan Yu
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Fusheng Han
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Hua He
- Cardiac Division of Emergency Intensive Care Unit, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
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12
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Liu C, Li C. C-reactive protein and cardiovascular diseases: a synthesis of studies based on different designs. Eur J Prev Cardiol 2023; 30:1593-1596. [PMID: 37079296 PMCID: PMC11483225 DOI: 10.1093/eurjpc/zwad116] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/10/2023] [Accepted: 04/13/2023] [Indexed: 04/21/2023]
Affiliation(s)
- Chunyu Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Chihua Li
- Survey Research Center, Institute for Social Research, University of Michigan, MI, USA
- Department of Epidemiology, School of Public Health, University of Michigan, MI, USA
- Department of Epidemiology, School of Public Health, Johns Hopkins Bloomberg School of Public Health, MD, USA
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13
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Wang L, Yang L, Liu H, Pu J, Li Y, Tang L, Chen Q, Pu F, Bai D. C-Reactive Protein Levels and Cognitive Decline following Acute Ischemic Stroke: A Systematic Review and Meta-Analysis. Brain Sci 2023; 13:1082. [PMID: 37509012 PMCID: PMC10377587 DOI: 10.3390/brainsci13071082] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/12/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.
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Affiliation(s)
- Likun Wang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Lining Yang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Haiyan Liu
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Juncai Pu
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yi Li
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Lu Tang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Qing Chen
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Fang Pu
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Dingqun Bai
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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14
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AlSharief M, Alabdurubalnabi E. Periodontal Pathogens and Adverse Pregnancy Outcomes: A Narrative Review. Life (Basel) 2023; 13:1559. [PMID: 37511934 PMCID: PMC10381683 DOI: 10.3390/life13071559] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 06/30/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
Periodontal disease is a multi-microbial infection of the teeth-supporting apparatus that manifests as clinical attachment loss and alveolar bone loss. The association between periodontal disease and systemic diseases has been proposed in the literature owing to the former's chronic state of inflammation, and adverse pregnancy outcomes are no exception. As a result of periodontal pathogen invasion, a series of systemic inflammatory and immunologic events affecting the safety of the fetoplacental unit may unfold. This may be further exaggerated by physiologic hormonal and metabolic fluctuations during pregnancy. This can not only negatively affect the gestation period and consequently cause preterm low weight but also complicate the pregnancy via preeclampsia and gestational diabetes. This narrative review article aims to provide a summary of relevant available evidence pertinent to the relationship between periodontal diseases, associated periodontal pathogens and virulence mechanisms mediated by pro-inflammatory cytokines and prostaglandins, and adverse pregnancy outcomes. Furthermore, this article highlights some of the literature addressing the impact of periodontal therapy interventions and pregnancy outcomes.
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Affiliation(s)
- Mishali AlSharief
- Department of Preventive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
| | - Esraa Alabdurubalnabi
- Fellowship in Periodontics Program, College of Dentistry, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
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15
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Mirolyubova O, Kholmatova K, Postoeva A, Kostrova G, Malyutina S, Kudryavtsev AV. Socio-Demographic, Lifestyle, and Cardiometabolic Characteristics Associated with Low-Grade Systemic Inflammation in Russian Adult Population. Biomolecules 2023; 13:biom13050835. [PMID: 37238705 DOI: 10.3390/biom13050835] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/08/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Mortality from cardiovascular diseases (CVDs) is higher in Russia compared to other European countries. High-sensitivity C-reactive protein (hs-CRP) is a biomarker of inflammation, and its elevated levels indicate increased CVD risks. We aim to describe the prevalence of low-grade systemic inflammation (LGSI) and the associated factors in a Russian population. The Know Your Heart cross-sectional study was conducted in Arkhangelsk, Russia in 2015-2017 with a population sample aged 35-69 years (n = 2380). LGSI was defined as hs-CRP ≥ 2 and <10 mg/L, and its associations with socio-demographic, lifestyle, and cardiometabolic characteristics were analyzed. The prevalence of LGSI (age-standardized to European Standard Population 2013) was 34.1% (33.5% in men and 36.1% in women). In the total sample, the increased odds ratios (ORs) of LGSI were associated with abdominal obesity (2.1), smoking (1.9), dyslipidemia (1.5), pulmonary diseases (1.4), and hypertension (1.3); the decreased ORs were in women (0.6) and in married participants (0.6). In men, the ORs were higher with abdominal obesity (2.1), smoking (2.0), CVDs (1.5), and hazardous drinking (1.5); in women-with abdominal obesity (4.4) and pulmonary diseases (1.5). In conclusion, one-third of the adult population in Arkhangelsk had LGSI. Abdominal obesity was the strongest LGSI correlate in both sexes, while the profiles of other associated factors were different between men and women.
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Affiliation(s)
- Olga Mirolyubova
- Department of Faculty Therapy, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Kamila Kholmatova
- International Research Competence Centre, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Hospital Therapy and Endocrinology, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037 Tromsø, Norway
| | - Anna Postoeva
- Department of Hospital Therapy and Endocrinology, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Galina Kostrova
- Department of Normal Physiology, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Sofia Malyutina
- Research Institute of Internal and Preventive Medicine, Branch of Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630008, Russia
- Department of Therapy, Hematology and Transfusiology, Novosibirsk State Medical University, Novosibirsk 630091, Russia
| | - Alexander V Kudryavtsev
- International Research Competence Centre, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037 Tromsø, Norway
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16
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Wang S, Han Y, Zhao H, Han X, Yin Y, Wu J, Zhang Y, Zeng X. Association between Coffee Consumption, Caffeine Intake, and Metabolic Syndrome Severity in Patients with Self-Reported Rheumatoid Arthritis: National Health and Nutrition Examination Survey 2003-2018. Nutrients 2022; 15:nu15010107. [PMID: 36615765 PMCID: PMC9824592 DOI: 10.3390/nu15010107] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/19/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Rheumatoid arthritis (RA) is chronic inflammatory disease. Although coffee impacts metabolism, no evidence has shown an association between coffee consumption and decreased risk for developing metabolic syndrome (MetS) among RA patients. Hence, we examined the association between coffee consumption and metabolic syndrome severity among 1094 participants with self-reported RA. Accordingly, patients with MetS z-scores of <0 and ≥0 were designated as low- and high-risk groups, respectively. In the fully adjusted model, drinking over two cups of coffee daily was associated with a decrease in the MetS z-score (p = 0.04). Subgroup analysis showed that in the low-risk group, daily intake of <2 cups of coffee was associated with low MetS z-scores (p = 0.003), scores (p = 0.03). Coffee intake was associated with low body mass index (p = 0.03 for 0−2 cups per day; p = 0.02 for >2 cups per day) and low HOMA-IR (β, −2.62; 95%CI, −5.13 to −0.11; p = 0.04). Our study suggests that coffee, but not decaffeinated coffee consumption and total caffeine intake, is associated with MetS severity in RA.
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17
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BMI Modifies Increased Mortality Risk of Post-PCI STEMI Patients with AKI. J Clin Med 2022; 11:jcm11206104. [PMID: 36294425 PMCID: PMC9604849 DOI: 10.3390/jcm11206104] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/29/2022] [Accepted: 10/13/2022] [Indexed: 11/25/2022] Open
Abstract
Mortality from acute ST elevation myocardial infarction (STEMI) was significantly reduced with the introduction of percutaneous catheterization intervention (PCI) but remains high in patients who develop acute kidney injury (AKI). Previous studies found overweight to be protective from mortality in patients suffering from STEMI and AKI separately but not as they occur concurrently. This study aimed to establish the relationship between AKI and mortality in STEMI patients after PCI and whether body mass index (BMI) has a protective impact. Between January 2008 and June 2016, two thousand one hundred and forty-one patients with STEMI underwent PCI and were admitted to the Tel Aviv Medical Center Cardiac Intensive Care Unit. Their demographic, laboratory, and clinical data were collected and analyzed. We compared all-cause mortality in patients who developed AKI after PCI for STEMI and those who did not. In total, 178 patients (10%) developed AKI and had higher mortality (p < 0.001). Logistic regression analysis was performed to determine the relationship between AKI, BMI, and mortality. AKI was significantly associated with both 30-day and overall mortality, while BMI had a significant protective effect. Survival analysis found a significant difference in 30-day and overall survival between patients with and without AKI with a significant protective effect of BMI on survival at 30 days. AKI presents a major risk for mortality and poor survival after PCI for STEMI, yet a beneficial effect of increased BMI modifies it.
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18
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Sevdımbas S, Satar S, Gulen M, Acehan S, Acele A, Koksaldı Sahin G, Aka Satar D. Blood urea nitrogen/albumin ratio on admission predicts mortality in patients with non ST segment elevation myocardial infarction. Scandinavian Journal of Clinical and Laboratory Investigation 2022; 82:454-460. [PMID: 36128642 DOI: 10.1080/00365513.2022.2122075] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The aim of this study is to reveal the predictive power of biomarkers and SYNTAX (SX) score for short-term mortality in patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) in the emergency department. This is prospective observational cohort study. Demographic characteristics of the patients, laboratory parameters on admission, left ventricular ejection fraction (LVEF) percentages, affected vessels in angiography (CAG) and the treatment strategy [medical therapy, percutaneous transluminal coronary angioplasty (PTCA), coronary angio by-pass graft] and SX scores were recorded on the data collection form. ROC curve was used to investigate the predictivity of blood urea nitrogen/albumin ratio (BAR), procalcitonin, C-reactive protein (CRP), high sensitivity cardiac troponin I (Hs-cTnI), CRP to serum albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and SX scores in mortality. Multivariate analysis of biomarkers and SX score was performed to estimate the patients' 30-day mortality. Of the 415 patients were included in the study. ROC analysis of BAR, CAR, CRP, Procalcitonin, Hs-cTnI, NLR and SX score to predict mortality was statistically significant. BAR (OR: 1.280, 95% CI: 1.113-1.472, p = .001) and SX score (OR: 1.071, 95% CI: 1.018-1.126, p = .007) were found to be independent predictors of 30 days mortality. LVEF reduction, SX score, the number of affected vessels and the frequency of LMCA lesions increase were found to be statistically significant in patients with BAR ≥4.8. BAR, which can be calculated easily and quickly on admission to the emergency department and in clinical practice, may be used to predict mortality in patients with NSTEMI.
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Affiliation(s)
- Sarper Sevdımbas
- Health Sciences University, Adana City Training and Research Hospital, Emergency Medicine Clinic, Adana, Turkey
| | - Salim Satar
- Health Sciences University, Adana City Training and Research Hospital, Emergency Medicine Clinic, Adana, Turkey
| | - Muge Gulen
- Health Sciences University, Adana City Training and Research Hospital, Emergency Medicine Clinic, Adana, Turkey
| | - Selen Acehan
- Health Sciences University, Adana City Training and Research Hospital, Emergency Medicine Clinic, Adana, Turkey
| | - Armagan Acele
- Health Sciences University, Adana City Training and Research Hospital, Department of Cardiology, Adana, Turkey
| | - Gonca Koksaldı Sahin
- Health Sciences University, Adana City Training and Research Hospital, Emergency Medicine Clinic, Adana, Turkey
| | - Deniz Aka Satar
- Health Sciences University, Adana City Training and Research Hospital, Assisted Reproduction Unit, Andrology Laboratory, Adana, Turkey
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19
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Bao M, Song Y, Wu S, Li J. Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy. J Cardiovasc Pharmacol 2022; 80:62-69. [PMID: 35384909 PMCID: PMC9249075 DOI: 10.1097/fjc.0000000000001267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/06/2022] [Indexed: 11/25/2022]
Abstract
ABSTRACT Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0-6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect ( P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.
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Affiliation(s)
- Minghui Bao
- Department of Cardiology, Peking University First Hospital, Peking University, Beijing, China
| | - Yongjian Song
- Department of Cardiology, Zhangjiakou First Hospital, Hebei, China; and
| | - Shouling Wu
- Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, Tangshan, China
| | - Jianping Li
- Department of Cardiology, Peking University First Hospital, Peking University, Beijing, China
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20
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Wallukat G, Mattecka S, Wenzel K, Schrödl W, Vogt B, Brunner P, Sheriff A, Kunze R. C-Reactive Protein (CRP) Blocks the Desensitization of Agonistic Stimulated G Protein Coupled Receptors (GPCRs) in Neonatal Rat Cardiomyocytes. J Clin Med 2022; 11:jcm11041058. [PMID: 35207331 PMCID: PMC8878432 DOI: 10.3390/jcm11041058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 02/04/2023] Open
Abstract
Recently, C-reactive protein (CRP) was shown to affect intracellular calcium signaling and blood pressure in vitro and in vivo, respectively. The aim of the present study was to further investigate if a direct effect on G-protein coupled receptor (GPCR) signaling by CRP can be observed by using CRP in combination with different GPCR agonists on spontaneously beating cultured neonatal rat cardiomyocytes. All used agonists (isoprenaline, clenbuterol, phenylephrine, angiotensin II and endothelin 1) affected the beat rate of cardiomyocytes significantly and after washing them out and re-stimulation the cells developed a pronounced desensitization of the corresponding receptors. CRP did not affect the basal beating-rate nor the initial increase/decrease in beat-rate triggered by different agonists. However, CRP co-incubated cells did not exhibit desensitization of the respective GPCRs after the stimulation with the different agonists. This lack of desensitization was independent of the GPCR type, but it was dependent on the CRP concentration. Therefore, CRP interferes with the desensitization of GPCRs and has to be considered as a novel regulator of adrenergic, angiotensin-1 and endothelin receptors.
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Affiliation(s)
- Gerd Wallukat
- Berlin Cures GmbH, BBB Campus, 13125 Berlin, Germany; (G.W.); (K.W.)
| | - Stephan Mattecka
- Pentracor GmbH, 16761 Hennigsdorf, Germany; (S.M.); (B.V.); (P.B.); (A.S.)
| | - Katrin Wenzel
- Berlin Cures GmbH, BBB Campus, 13125 Berlin, Germany; (G.W.); (K.W.)
| | - Wieland Schrödl
- Institute of Bacteriology and Mycology Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany;
| | - Birgit Vogt
- Pentracor GmbH, 16761 Hennigsdorf, Germany; (S.M.); (B.V.); (P.B.); (A.S.)
| | - Patrizia Brunner
- Pentracor GmbH, 16761 Hennigsdorf, Germany; (S.M.); (B.V.); (P.B.); (A.S.)
| | - Ahmed Sheriff
- Pentracor GmbH, 16761 Hennigsdorf, Germany; (S.M.); (B.V.); (P.B.); (A.S.)
- Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité University Medicine, 12200 Berlin, Germany
| | - Rudolf Kunze
- Pentracor GmbH, 16761 Hennigsdorf, Germany; (S.M.); (B.V.); (P.B.); (A.S.)
- Correspondence:
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21
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C-Reactive Protein Levels in relation to Incidence of Hypertension in Chinese Adults: Longitudinal Analyses from the China Health and Nutrition Survey. Int J Hypertens 2021; 2021:3326349. [PMID: 34925916 PMCID: PMC8683184 DOI: 10.1155/2021/3326349] [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: 09/27/2021] [Accepted: 11/25/2021] [Indexed: 01/28/2023] Open
Abstract
Objective To explore the association between high sensitivity C-reactive protein (hs-CRP) levels and incident hypertension, as well as the association between hs-CRP levels and related covariates, in a Chinese adult population. Methods This study was based on the China Health and Nutrition Survey, a continuing open, large-scale prospective cohort study. Adult participants who were free of hypertension were included at baseline survey in 2009 and were followed up in 2015 (follow-up rate: 77.45%). The hs-CRP was measured using the immunoturbidimetric method and divided into three groups: low-risk group (0 ≤ hs-CRP <1 mg/L), average-risk group (1 ≤ hs-CRP <3 mg/L), and high-risk group (3 ≤ hs-CRP ≤10 mg/L). Definite diagnosis of hypertension in the follow-up survey in 2015 was the endpoint event of this study. The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve analyses were used to evaluate the predictive value of the hs-CRP. Results 3794 participants were finally included as study sample, of whom 912 developed hypertension during a 6-year follow-up period (incidence: 24.1%). The incidences of hypertension in hs-CRP low-risk, average-risk, and high-risk groups were 17.6% (200/1135), 25.9% (521/2015), and 29.7% (191/644), respectively. Spearman's correlation analyses showed that there was significant positive correlation between hs-CRP levels and waist circumference, total triglycerides, total cholesterol, age, body mass index, and homeostasis model assessment of insulin resistance index. Stepwise regression analyses showed that participants in the hs-CRP high-risk group had a 46.2% higher risk of developing hypertension compared with those in the hs-CRP low-risk group (odds ratio: 1.462, 95% confidence interval: 1.018–2.101). Baseline systolic and diastolic blood pressure levels and waist circumference contributed the most to the development of hypertension with R2 of 0.076, 0.052, and 0.039, respectively, while hs-CRP had lower area under the curve (AUC) for hypertension, adding baseline BP and WC to the prediction model increased the AUC to 0.708 (95% CI: 0.681–0.735). Conclusion This study revealed a weak positive association between CRP levels and future incidence of hypertension in the Chinese population. The combination of hs-CRP with baseline BP and waist circumference (WC) had a higher predictive value for hypertension (AUC: 0.708), but the predictive value was still limited.
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22
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C-Reactive Protein Level Predicts Cardiovascular Risk in Chinese Young Female Population. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6538079. [PMID: 34900087 PMCID: PMC8654566 DOI: 10.1155/2021/6538079] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 11/16/2021] [Indexed: 11/24/2022]
Abstract
Background C-reactive protein (CRP) is one of the most common oxidative indexes affected by many diseases. In recent years, there have been many studies on CRP, but the relationship between CRP levels and the cardiovascular risk in the Chinese young female population is still unclear. The purpose of this work is to explore the predictive value of CRP for the cardiovascular risk in the Chinese young female population. Methods The study is conducted by 1 : 1 case-control to retrospectively analyze 420 young women with acute coronary syndrome (ACS group) who underwent percutaneous coronary intervention (PCI) and 420 young women (control group) who underwent coronary angiography (CAG) to exclude coronary heart disease from January 2007 to December 2016. All patients are divided into three subgroups according to CRP values: subgroup 1: CRP < 1.0 mg/L (n = 402); subgroup 2: 1.0 mg/L ≤ CRP ≤ 3.0 mg/L (n = 303); subgroup 3: CRP > 3.0 mg/L (n = 135). The levels of CRP were observed in the two groups and three subgroups. Results A total of 840 patients were analyzed. The mean duration of follow-up was 66.37 ± 30.06 months. The results showed that the level of CRP in the ACS group was significantly higher than that in the control group (1.30 ± 1.70 vs. 3.33 ± 5.92, respectively, p < 0.001), and patients with higher CRP levels were associated with a significantly increased rate of major adverse cardiovascular events (MACE) (7.0% vs. 8.9% vs. 19.30%, respectively, p < 0.05). After adjustment for baseline covariates, CRP level was still an independent predictor for the incidence of MACE, either as a continuous variable or as a categorical variable. There was a significantly higher rate of all-cause mortality and myocardial infarction in patients with higher CRP values during follow-up. Conclusions The research results show that high CRP is associated with increased risk of ACS in the Chinese young female population. Risk stratification with CRP as an adjunct to predict clinical risk factors might be useful in the Chinese young female population.
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Speer H, D'Cunha NM, Naumovski N, McKune AJ. Sex, Age, BMI, and C-Reactive Protein Impact the Odds of Developing Hypertension-Findings Based on Data From the Health and Retirement Study (HRS). Am J Hypertens 2021; 34:1057-1063. [PMID: 34106249 DOI: 10.1093/ajh/hpab088] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 04/22/2021] [Accepted: 06/03/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Hypertension is a major contributor to cardiovascular diseases and premature death, therefore determining factors that contribute to such a high burden of disease is critically important. This study examined anthropometric and physical measurements, as well as blood and saliva biomarkers, as predictors for hypertension using datasets from the 2008 Health and Retirement Study. METHODS A total of 2,924 participants (aged 74.84 ± 6.45 years) were included. Binary logistic regression was performed to ascertain the effects of sex, age, telomere length, C-reactive protein (CRP), body mass index (BMI), and additional markers on the odds of developing hypertension. RESULTS Males had 2.3 times the odds (odds ratio (OR) = 2.313, confidence interval (CI) 95% (1.391, 3.845); P = 0.001) of being hypertensive if they were obese, females had 1.7 times the odds (OR = 1.788, CI 95% (1.260, 2.536); P = 0.001) if overweight, and 2.4 times (OR = 2.479, CI 95% (1.693, 3.630); P < 0.001) if obese. Age in females was an independent predictor where every 1-year increase in age was tied to a 5.1% increase in being hypertensive (OR = 1.051, CI 95% (1.027, 1.075); P <0.001), and CRP (>3 mg/l) had 1.4 times the odds (OR = 1.447, CI 95% (1.079, 1.942); P = 0.014). CONCLUSIONS This study provides verification for BMI as a predictor for hypertension and proposes age and CRP as predictors for females. Specific sex differences and life stage should be considered when evaluating hypertension risk to improve clinical outcomes and promote healthy aging.
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Affiliation(s)
- Hollie Speer
- Faculty of Science and Technology, School of Science, University of Canberra, Bruce, ACT, Australia
- Faculty of Health, School of Rehabilitation and Exercise Sciences, University of Canberra, Bruce, ACT, Australia
- University of Canberra Research Institute for Sport and Exercise (UCRISE), University of Canberra, Bruce, ACT, Australia
| | - Nathan M D'Cunha
- Faculty of Health, School of Rehabilitation and Exercise Sciences, University of Canberra, Bruce, ACT, Australia
- Functional Foods and Nutrition Research (FFNR) Laboratory, University of Canberra, Bruce, ACT, Australia
| | - Nenad Naumovski
- Faculty of Health, School of Rehabilitation and Exercise Sciences, University of Canberra, Bruce, ACT, Australia
- Functional Foods and Nutrition Research (FFNR) Laboratory, University of Canberra, Bruce, ACT, Australia
- Discipline of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | - Andrew J McKune
- Faculty of Health, School of Rehabilitation and Exercise Sciences, University of Canberra, Bruce, ACT, Australia
- University of Canberra Research Institute for Sport and Exercise (UCRISE), University of Canberra, Bruce, ACT, Australia
- Discipline of Biokinetics, Exercise and Leisure Sciences, School of Health Science, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
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Todorov SS, Deribas VJ, Kazmin AS, Todorov SS. [Morphological and Molecular-Biological Changes in the Coronary Arteries after Stenting]. ACTA ACUST UNITED AC 2021; 61:79-84. [PMID: 34397345 DOI: 10.18087/cardio.2021.7.n1211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/10/2020] [Accepted: 07/29/2020] [Indexed: 11/18/2022]
Abstract
This review addresses morphological changes in coronary arteries following stenting, which result from damage to the vascular wall. These changes include 1) formation of a thrombus in the site of intimal injury; 2) inflammation; 3) proliferation and migration of smooth muscle cells; 4) formation of extracellular matrix. Each of these pathological processes has specific morpho-biological features. The review shows the role of von Willebrand factor in development of early thrombosis after intimal injury, which provokes activation of the inflammatory response followed by proliferation of smooth muscle cell that synthetize the extracellular matrix. These cellular and intercellular changes are based on overexpression of TGF-β1 protein, which facilitates modulation of various types of smooth muscle cells, including contractile and secretory ones. Issues of fine regulation of cellular and intercellular interactions by apoptosis, activation of mTOR signaling molecules, and microRNA are still understudied. Dynamic changes in drug-coated stents during development of neoatherosclerosis and late thrombosis remain not elucidated. Current reports show that initial mechanisms triggering pathological regenerative and hyperplastic processes that result in coronary restenosis in the area of implanted stents may form early (first hours or days) after stenting. Most studies were performed on experimental rather than on autopsy material, which does not allow fully unbiased interpretation of obtained data. Studying dynamics of morphological and molecular changes in coronary arteries after stenting, including on autopsy material, will allow one to express an opinion on the risk of postoperative thrombosis and restenosis.
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Affiliation(s)
- S S Todorov
- Rostov State Medical University of the Ministry of Health of Russia, Rostov-on-Don
| | - V J Deribas
- Rostov State Medical University of the Ministry of Health of Russia, Rostov-on-Don
| | - A S Kazmin
- Rostov State Medical University of the Ministry of Health of Russia, Rostov-on-Don
| | - S S Todorov
- Rostov State Medical University of the Ministry of Health of Russia, Rostov-on-Don
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Abstract
Neurohormones and inflammatory mediators have effects in both the heart and the peripheral vasculature. In patients with heart failure (HF), neurohormonal activation and increased levels of inflammatory mediators promote ventricular remodeling and development of HF, as well as vascular dysfunction and arterial stiffness. These processes may lead to a vicious cycle, whereby arterial stiffness perpetuates further ventricular remodeling leading to exacerbation of symptoms. Although significant advances have been made in the treatment of HF, currently available treatment strategies slow, but do not halt, this cycle. The current treatment for HF patients involves the inhibition of neurohormonal activation, which can reduce morbidity and mortality related to this condition. Beyond benefits associated with neurohormonal blockade, other strategies have focused on inhibition of inflammatory pathways implicated in the pathogenesis of HF. Unfortunately, attempts to target inflammation have not yet been successful to improve prognosis of HF. Further work is required to interrupt key maladaptive mechanisms involved in disease progression.
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Poznyak AV, Bharadwaj D, Prasad G, Grechko AV, Sazonova MA, Orekhov AN. Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD. Int J Mol Sci 2021; 22:ijms22136702. [PMID: 34206708 PMCID: PMC8269397 DOI: 10.3390/ijms22136702] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/18/2021] [Accepted: 06/18/2021] [Indexed: 12/25/2022] Open
Abstract
Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.
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Affiliation(s)
- Anastasia V. Poznyak
- Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia
- Correspondence: (A.V.P.); (A.N.O.)
| | - Dwaipayan Bharadwaj
- Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi 110067, India;
- Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India;
| | - Gauri Prasad
- Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India;
| | - Andrey V. Grechko
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 14-3 Solyanka Street, 109240 Moscow, Russia;
| | - Margarita A. Sazonova
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia;
| | - Alexander N. Orekhov
- Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia;
- Institute of Human Morphology, 3 Tsyurupa Street, 117418 Moscow, Russia
- Correspondence: (A.V.P.); (A.N.O.)
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Wendelstein J, Fuchs B, Schlittgen S, Zielke R, Brünner J, Bolz M, Alten R, Erb C. Influence of ACPA-positive rheumatoid arthritis on visual field testing in patients with arterial hypertension: A comparative cross-sectional study. Ophthalmic Physiol Opt 2021; 41:941-948. [PMID: 34076910 PMCID: PMC8252444 DOI: 10.1111/opo.12838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 04/15/2021] [Indexed: 11/29/2022]
Abstract
Purpose To evaluate a possible influence of anti‐cyclic citrullinated peptide autoantibodies (ACPA) ‐ positive rheumatoid arthritis (RA) on visual field (VF) testing in patients with arterial hypertension (aHT). Methods We conducted an observational cross‐sectional study comparing patients with ACPA‐positive RA and aHT, patients with aHT and healthy subjects. Further inclusion criteria were visual acuity (VA) of 0.8 or better and age between 40 and 60 years. VF testing was performed with standard automated achromatic perimetry (SAP), short wavelength automated perimetry (SWAP) (Octopus 300®) and flicker perimetry (Pulsar®). Results were analysed for a possible correlation with blood pressure or RA‐activity. Results Twenty subjects with RA and aHT, 26 patients with aHT and 22 healthy participants were examined. Significant differences were found for mean sensitivity (MS) in SWAP comparing RA‐patients with healthy participants (ΔMS −3.06, p = 0.001) and with hypertensive patients (ΔMS −2.32, p = 0.007). In SAP we observed a significant difference between patients with RA and healthy subjects regarding loss variance (LV) (ΔLV = +9.77, p = 0.004). Flicker perimetry did not demonstrate significant differences between groups. A correlation of VF changes with blood pressure level or RA‐activity was not observed. Conclusion Patients with ACPA‐positive RA and aHT showed significant impairment of VF performance in SWAP compared to patients with aHT alone and healthy subjects. SAP also revealed a significant difference of LV between RA‐patients and healthy subjects. aHT does not seem to induce functional changes in VF testing alone.
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Affiliation(s)
- Jascha Wendelstein
- Department of Ophthalmology and Optometry, Kepler University Hospital, Linz, Austria.,Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Barbara Fuchs
- Department of Ophthalmology and Optometry, Kepler University Hospital, Linz, Austria.,Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Sarah Schlittgen
- Department of Oncology, Clinical Centre of Havelhöhe, Berlin, Germany
| | - Robert Zielke
- Group Practice for General Medicine Jüterbog, Jüterbog, Germany
| | | | - Matthias Bolz
- Department of Ophthalmology and Optometry, Kepler University Hospital, Linz, Austria.,Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Rielke Alten
- Department of Rheumatology, Schlosspark Klinik, Berlin, Germany
| | - Carl Erb
- Eye Clinic at Wittenbergplatz, Berlin, Germany
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28
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Abdelmaseih R, Alsamman MM, Faluk M, Hasan SM. Cardiovascular Outcomes With Anti-Inflammatory Therapies: Review of Literature. Curr Probl Cardiol 2021; 47:100840. [PMID: 33994031 DOI: 10.1016/j.cpcardiol.2021.100840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 03/08/2021] [Indexed: 11/03/2022]
Abstract
Inflammation is a major contributing factor in the development of cardiovascular disease (CVD) and has been a popular topic of discussion as it provides a potential therapeutic target to reduce disease progression. Multiple inflammatory markers have been linked with progressive atherosclerosis which includes interleukin-6, tumor necrosis factor-α, C-reactive protein amongst others, this article aims to review current literature to evaluate the effectiveness of anti-inflammatory therapies in cardiovascular disease.
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Affiliation(s)
- Ramy Abdelmaseih
- University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL; Ocala Regional Medical Center, Internal Medicine Residency Program, Ocala, FL.
| | - M Mrhaf Alsamman
- University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL; Ocala Regional Medical Center, Internal Medicine Residency Program, Ocala, FL
| | - Mohammad Faluk
- University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL; Ocala Regional Medical Center, Internal Medicine Residency Program, Ocala, FL
| | - Syed Mustajab Hasan
- University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL; Ocala Regional Medical Center, Internal Medicine Residency Program, Ocala, FL
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Yayla C, Gayretli Yayla K. C-Reactive Protein to Albumin Ratio in Patients With Saphenous Vein Graft Disease. Angiology 2021; 72:770-775. [PMID: 33678042 DOI: 10.1177/0003319721998863] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Atherosclerosis plays an important role in saphenous vein graft disease (SVGD). Previous studies showed that inflammatory blood cells play an active role in this process. C-reactive protein to albumin ratio (CAR) is considered as a novel predictor for cardiovascular risk and an indicator of inflammation. We aimed to assess the relationship between SVGD and CAR. A total of 711 participants with saphenous vein graft (SVG) were included; 348 patients had SVGD and 363 patients had patent (no stenosis) SVG. C-reactive protein to albumin ratio was higher in patients with SVGD (P < .001). There was a significant positive correlation between CAR and the age of SVG (r = 0.123; P = .001) and SYNTAX score (r = 0.568; P < .001). Multivariate logistic regression analyses showed that lymphocyte count, CAR, and SYNTAX score were independent predictors of SVGD (P < .05). C-reactive protein to albumin ratio may be a useful marker after bypass surgery to predict SVGD.
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Affiliation(s)
- Cagri Yayla
- Department of Cardiology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Kadriye Gayretli Yayla
- Department of Cardiology, Dr. Abdurrahman Yurtaslan Ankara Onkoloji Education and Research Hospital, University of Health Sciences, Ankara, Turkey
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30
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Bisaria S, Terrigno V, Hunter K, Roy S. Association of Elevated Levels of Inflammatory Marker High-Sensitivity C-Reactive Protein and Hypertension. J Prim Care Community Health 2020; 11:2150132720984426. [PMID: 33356789 PMCID: PMC7768830 DOI: 10.1177/2150132720984426] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Introduction The correlation between inflammation and vascular disease is widely accepted. High levels of C-reactive protein (CRP) have been shown to play a role in the process of endothelial dysfunction. Hypertension is described as an inflammatory vascular disease, and is 1 of the most commonly encountered diseases in the outpatient setting. We studied the association between the elevated high sensitivity-CRP (hs-CRP) level and hypertension, as well as other comorbid conditions. Methods Electronic medical records of 169 adult patients in our internal medicine office were reviewed for hs-CRP levels, and divided into 2 groups: elevated hs-CRP (≥2 mg/L; n = 110) and normal hs-CRP (<2 mg/L; n = 59). Independent T-Test was used to compare the means of continuous variables between the groups if they were normally distributed. Mann Whitney U-Test was used to compare the continuous variables that were non-parametric. Logistic regression was used to compare the dependent and independent variables. Results Among subjects with elevated hs-CRP, 58.2% had hypertension while 47.5% of subjects with normal hs-CRP levels had hypertension (P = .182). There were higher frequencies of association of coronary artery disease (CAD), cerebrovascular disease and hypothyroidism in elevated hs-CRP group but the differences were not statistically significant. Mean white blood cell count was statistically higher in elevated hs-CRP group (P < .05), while alcohol use was significantly higher (P < .05) and statin use was higher in the normal hs-CRP group. There was an inverse relationship between HDL-C and hs-CRP. Conclusions There was no statistically significant correlation between hs-CRP level and hypertension. Hs-CRP has statistically significant associations between alcohol use, dementia, white blood cell count, and HDL levels. Promising but not statistically significant correlations were observed between hs-CRP and statin therapy, hypothyroidism, coronary artery disease, and cerebrovascular disease.
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Affiliation(s)
- Sharmila Bisaria
- Cooper Medical School of Rowan University, Cooper University Health Care, Department of Medicine, Camden, New Jersey, USA
| | - Vittorio Terrigno
- Cooper Medical School of Rowan University, Cooper University Health Care, Department of Medicine, Camden, New Jersey, USA
| | - Krystal Hunter
- Cooper Research Institute, Cooper Medical School of Rowan University, Camden, New Jersey, USA
| | - Satyajeet Roy
- Cooper Medical School of Rowan University, Cooper University Health Care, Department of Medicine, Camden, New Jersey, USA
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Nejat R, Sadr AS. Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study. In Silico Pharmacol 2020; 9:1. [PMID: 33294307 PMCID: PMC7716628 DOI: 10.1007/s40203-020-00058-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/04/2020] [Indexed: 12/13/2022] Open
Abstract
Proposing a theory about the pathophysiology of cytokine storm in COVID19, we were to find the potential drugs to treat this disease and to find any effect of these drugs on the virus infectivity through an in silico study. COVID-19-induced ARDS is linked to a cytokine storm phenomenon not explainable solely by the virus infectivity. Knowing that ACE2, the hydrolyzing enzyme of AngII and SARS-CoV2 receptor, downregulates when the virus enters the host cells, we hypothesize that hyperacute AngII upregulation is the eliciting factor of this ARDS. We were to validate this theory through reviewing previous studies to figure out the role of overzealous activation of AT1R in ARDS. According to this theory losartan may attenuate ARDS in this disease. Imatinib, has previously been elucidated to be promising in modulating lung inflammatory reactions and virus infectivity in SARS and MERS. We did an in silico study to uncover any probable other unconsidered inhibitory effects of losartan and imatinib against SARS-CoV2 pathogenesis. Reviewing the literature, we could find that over-activation of AT1R could explain precisely the mechanism of cytokine storm in COVID19. Our in silico study revealed that losartan and imatinib could probably: (1) decline SARS-CoV2 affinity to ACE2. (2) inhibit the main protease and furin, (3) disturb papain-like protease and p38MAPK functions. Our reviewing on renin-angiotensin system showed that overzealous activation of AT1R by hyper-acute excess of AngII due to acute downregulation of ACE2 by SARS-CoV2 explains precisely the mechanism of cytokine storm in COVID-19. Besides, based on our in silico study we concluded that losartan and imatinib are promising in COVID19.
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Affiliation(s)
- Reza Nejat
- Department of Anesthesiology and Critical Care Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Shahir Sadr
- Bioinformatics Research Center, Cheragh Medical Institute and Hospital, Kabul, Afghanistan
- Department of Computer Science, Faculty of Mathematical Sciences, Shahid Beheshti University, Tehran, Iran
- Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran
- School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran
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Ikonomidis I, Pavlidis G, Katsimbri P, Lambadiari V, Parissis J, Andreadou I, Tsoumani M, Boumpas D, Kouretas D, Iliodromitis E. Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19. Food Chem Toxicol 2020; 145:111694. [PMID: 32822775 PMCID: PMC7434461 DOI: 10.1016/j.fct.2020.111694] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/05/2020] [Accepted: 08/14/2020] [Indexed: 02/07/2023]
Abstract
We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. Clinical trial registration url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.
Tocilizumab improves endothelial glycocalyx and increases effective myocardial work. IL-6 inhibition significantly reduces the inflammatory burden and oxidative stress. Tocilizumab may have favorable effects on diseases with excess IL-6 release.
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Affiliation(s)
- Ignatios Ikonomidis
- 2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece.
| | - George Pavlidis
- 2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
| | - Pelagia Katsimbri
- 4th Department of Internal Medicine, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
| | - Vaia Lambadiari
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
| | - John Parissis
- 2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
| | - Ioanna Andreadou
- Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15741, Athens, Greece
| | - Maria Tsoumani
- Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15741, Athens, Greece
| | - Dimitrios Boumpas
- 4th Department of Internal Medicine, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
| | - Dimitrios Kouretas
- Department of Biochemistry and Biotechnology, University of Thessaly, 41500, Larissa, Greece
| | - Efstathios Iliodromitis
- 2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462, Athens, Greece
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Curcumin Suppresses Aldosterone-Induced CRP Generation in Rat Vascular Smooth Muscle Cells via Interfering with the ROS-ERK1/2 Signaling Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:3245653. [PMID: 32831861 PMCID: PMC7428966 DOI: 10.1155/2020/3245653] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 06/07/2020] [Accepted: 07/16/2020] [Indexed: 01/08/2023]
Abstract
Aldosterone regulates the initiation and development of atherosclerosis which is identified as a chronic inflammatory disease by promoting the generation of C-reactive protein in vascular smooth muscle cells. Curcumin is the most active ingredient of turmeric with anti-inflammation and antioxidation effects. Here, the effect of curcumin on aldosterone-induced C-reactive protein generation in vascular smooth muscle and the molecular mechanisms involved were explored. Primary rat vascular smooth muscle cells and hyperaldosteronism model rats were used in this study. The amount of C-reactive protein, reactive oxygen species, and the signaling pathway-related molecules generated were estimated. We found that curcumin inhibited aldosterone-induced C-reactive protein generation in vascular smooth muscle cells by interfering with the reactive oxygen species-ERK1/2 signal pathway. The results provide new evidence for the potential anti-inflammatory and cardiovascular protective effects of curcumin.
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Liu L. The anti-inflammatory effect of miR-16 through targeting C- reactive protein is regulated by HuR in vascular smooth muscle cells. Biochem Biophys Res Commun 2020; 528:636-643. [PMID: 32513543 DOI: 10.1016/j.bbrc.2020.05.104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 05/15/2020] [Indexed: 01/08/2023]
Abstract
Atherosclerosis (AS) is the main pathological basis of coronary heart disease (CHD). Vascular smooth muscle cells (VMSCs) proliferation, migration and inflammatory response are the cytopathologic basis of AS. MiR-16 has been suggested to be closely associated with cell proliferation and inflammation. The regulatory role of the RNA binding protein HuR on miR-16 has been reported in colon cancer. However, the underlying roles of miR-16 on VMSCs and the regulatory function of HuR on miR-16 in VMSCs remain unknown. In this study, we found that the expression of miR-16 reduced and the expression of C-reactive protein and HuR increased when contractile VSMCs transformed into synthetic VMSCs. Furthermore, miR-16 impeded cell proliferation and inflammation via targeting CRP in VMSCs. HuR down-regulated miR-16 expression and impeded its influence on VMSCs. This study might provide an opportunity to develop a new effective target for the treatment of CHD.
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Affiliation(s)
- Liang Liu
- Department of Cardiovasology, PKUCare Luzhong Hospital, No. 65, Taigong Road, Linzi District, 255400, Zibo, China.
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Fu Y, Wu Y, Liu E. C-reactive protein and cardiovascular disease: From animal studies to the clinic (Review). Exp Ther Med 2020; 20:1211-1219. [PMID: 32765664 PMCID: PMC7388508 DOI: 10.3892/etm.2020.8840] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 05/05/2020] [Indexed: 12/22/2022] Open
Abstract
C-reactive protein (CRP) and cardiovascular disease (CVD) have long been important research topics. CRP is an acute phase protein, while CVD is an inflammatory condition. The association between CRP and CVD remains controversial and has been attracting increasing attention. Traditionally, the main marker of CVD is considered to be low-density lipoprotein cholesterol. However, due to its unique characteristics, CRP may represent a novel marker or a new therapeutic target for CVD. Clinical studies have demonstrated that CRP is a predictor of CVD, but whether it is directly involved in the development and progression of CVD has yet to be fully elucidated. Recent clinical studies have demonstrated that lowering plasma CRP levels may reduce the incidence of CVD. The aim of the present review was to investigate the association between CRP and CVD, particularly atherosclerosis, from laboratory animal studies to clinical research.
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Affiliation(s)
- Yu Fu
- MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Yi Wu
- MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
| | - Enqi Liu
- Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
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Immunotherapy for the rheumatoid arthritis-associated coronary artery disease: promise and future. Chin Med J (Engl) 2020; 132:2972-2983. [PMID: 31855971 PMCID: PMC6964948 DOI: 10.1097/cm9.0000000000000530] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Objective: To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen. Data sources: This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation. Study selection: All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed. Results: RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect. Conclusions: RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.
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Pecoits–Filho R, Stenvinkel P, Wang AYM, Heimbürger O, Lindholm B. Chronic Inflammation in Peritoneal Dialysis: The Search for the Holy Grail? Perit Dial Int 2020. [DOI: 10.1177/089686080402400407] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Mortality and morbidity in chronic kidney disease (CKD) patients are unacceptably high. The annual mortality rate due to cardiovascular disease (CVD) is approximately 9%, which, for the middle-aged person, is at least 10- to 20-fold higher than for the general population. Classic risk factors for CVD are highly prevalent in CKD patients, but they cannot fully account for the excessive rate of CVD in this population. Instead, it has become increasingly clear that nontraditional risk factors, such as systemic inflammation, may play a key role in the development of atherosclerosis. It is well established that inflammatory markers are very powerful predictors of high CVD morbidity and mortality not only in the general population, but particularly in CKD patients. Signs of a sustained low-grade inflammation, such as increased levels of C-reactive protein (CRP), are present in the majority of stage 5 CKD patients, even in patients in clinically stable condition, and they are also commonly observed after the initiation of dialysis therapy. Dialysis therapy — hemodialysis as well as peritoneal dialysis (PD) — may itself contribute to systemic inflammation. Local intraperitoneal inflammation can also occur in patients treated with PD. These local effects may result in a low-grade inflammation, caused by the bioincompatibility of conventional glucose-based dialysis fluids, to intense inflammation associated with peritonitis. Given these circumstances, it is reasonable to hypothesize that strategies aiming to reduce inflammation are potentially important and novel, and could serve to reduce CVD, thereby lowering morbidity and mortality in patients with CKD. In this review we provide information supporting the hypothesis that systemic inflammation is tightly linked to the most common complications of CKD patients, in particular those on PD, and that local inflammation in PD may contribute to various related complications. The aims of this review are to discuss the reasons that make inflammation an attractive target for intervention in CKD, the particular aspects of the inflammation–CVD axis during PD treatment that are likely involved, and possible means for the detection and management of chronic inflammation in PD patients.
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Affiliation(s)
- Roberto Pecoits–Filho
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
- Centro de Ciências Biológicas e da Saúde, Pontifícia Universidade Católica do Paraná, and Renal Diabetes and Hypertension Research Center of the ProRenal Foundation, Curitiba, Brazil
| | - Peter Stenvinkel
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
| | - Angela Yee-Moon Wang
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Olof Heimbürger
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden
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Ayari F, Ben Chaaben A, Ben Ammar H, Nefzi R, Ouni N, Mihoub O, Abaza H, Aissa A, Douik H, Gara S, Larnaout A, Salmi A, Ben Ammar-El Gaaied A, Leboyer M, El Hechmi Z, Guemira F, Tamouza R. Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population. Encephale 2020; 46:241-247. [PMID: 31959465 DOI: 10.1016/j.encep.2019.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 09/23/2019] [Accepted: 10/07/2019] [Indexed: 12/13/2022]
Abstract
The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.
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Affiliation(s)
- F Ayari
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia.
| | - A Ben Chaaben
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - H Ben Ammar
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - R Nefzi
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - N Ouni
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - O Mihoub
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - H Abaza
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Aissa
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - H Douik
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - S Gara
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Larnaout
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - A Salmi
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - A Ben Ammar-El Gaaied
- Immunology Department, Faculty of Mathematics, Physics and Natural Sciences, Tunis El Manar University, Tunis, Tunisia
| | - M Leboyer
- Inserm U 955, FondaMental foundation, department of psychiatry, university hospital Mondor, AP-HP, 1006 Créteil, France
| | - Z El Hechmi
- Research Unit 03/04 Schizophrenia and Department of Psychiatry F, Razi Hospital, Mannouba, Tunisia
| | - F Guemira
- Clinical Biology Department, Salah Azaiz Institute, Tunis, Tunisia
| | - R Tamouza
- Inserm U 955, FondaMental foundation, department of psychiatry, university hospital Mondor, AP-HP, 1006 Créteil, France
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Sun W, Wu Y, Gao M, Tian Y, Qi P, Shen Y, Huang L, Shi L, Wang Y, Liu X. C-reactive protein promotes inflammation through TLR4/NF-κB/TGF-β pathway in HL-1 cells. Biosci Rep 2019; 39:BSR20190888. [PMID: 31391207 PMCID: PMC6712437 DOI: 10.1042/bsr20190888] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 07/25/2019] [Accepted: 08/02/2019] [Indexed: 01/08/2023] Open
Abstract
Atrial fibrillation (AF) is the most common type of heart arrhythmia. Currently, the pathogenesis of AF is not fully understood yet. A growing body of evidence highlighted the strong association between inflammation and the pathogenesis of AF. C-reactive protein (CRP) is an inflammation marker with increased expression in AF. Therefore, the aim of this study was to determine if CRP promotes inflammation, which may sequentially mediate the onset of AF and the concurrent atrial fibrosis, through TLR4/NF-κB/TGF-β pathway. HL-1 cells were treated with either 25 or 50 μg/ml recombinant human CRP. TGF-β1 and NF-κB inhibitors were given either solely or together to the 50 μg/ml CRP-treated cells. Cell proliferation, apoptosis, the expression of apoptotic factors and TLR4, IL-6, TGF-β1, Smad2, and the phosphorylation of Smad2 were determined. Data showed that CRP induced dose-dependent inhibition on cell proliferation and promoted cell apoptosis, which was induced through both intrinsic and extrinsic pathways. Such effects were reversed by inhibiting TGF-β1 and/or NF-κB. Inhibition of TGF-β1 and/or NF-κB also reduced the expression of TLR4 and IL-6. Inhibition of NF-κB alone weakened the expression of TGF-β1 and phosphorylation of Smad2. Our study demonstrated that CRP is not only a marker, but also an important mediator in the induction of inflammation and likely the pathogenesis of AF. We for the first time reported CRP-induced activation and cross-talk between TLR4 and NF-κB/TGF-β1 signaling pathway in a cardiomyocyte model. Reducing CRP and targeting TLR4/NF-κB/TGF-β1 pathway may provide new insights in the therapeutic interventions to inflammation-induced AF.
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Affiliation(s)
- Weiping Sun
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
- Department of Cardiology, Beijing Luhe Hospital, Capital Medical University, Beijing 100037, China
| | - Yongquan Wu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
| | - Mingyang Gao
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Ying Tian
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Peng Qi
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Yujing Shen
- Department of Cardiology, Fuwai Hospital, Chinese academy of Medicine sciences, Beijing 100037, China
| | - Lihong Huang
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Liang Shi
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Yanjiang Wang
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
| | - Xingpeng Liu
- Department of Cardiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100037, China
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Liu Y, Jia SD, Yao Y, Tang XF, Xu N, Jiang L, Gao Z, Chen J, Yang YJ, Gao RL, Xu B, Yuan JQ. Impact of high-sensitivity C-reactive protein on coronary artery disease severity and outcomes in patients undergoing percutaneous coronary intervention. J Cardiol 2019; 75:60-65. [PMID: 31416781 DOI: 10.1016/j.jjcc.2019.06.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 05/23/2019] [Accepted: 06/10/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Inflammation plays a pivotal role in coronary artery disease (CAD). Few data from large-size studies are available on the association of high-sensitivity C-reactive protein (hs-CRP) and severity of CAD. Our aim was to investigate their relationship as well as their impact on long-term outcomes in patients undergoing percutaneous coronary intervention. METHODS In 2013, 10,020 patients were consecutively included. Patients were divided into three groups based on hs-CRP on admission: 0-3mg/L (n=6978, 69.6%), 3.01-10mg/L (n=1997, 19.9%), >10mg/L (n=1045, 10.4%). Disease severity was determined by SYNTAX score (SS). Their differences were assessed in SS and major adverse cardiovascular events (MACEs, including all-cause death, myocardial infarction, revascularization, and in-stent thrombosis) among groups. RESULTS The mean follow-up period was 874 days. Patients with elevated hs-CRP were older, had more risk factors such as hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, and cigarette smoking. Multivariate regression analysis showed that hs-CRP >10mg/L (OR 1.49, 95% confidence interval 1.21-1.84, p<0.001), age, previous myocardial infarction, serum creatinine, and left ventricular ejection fraction were independent predictors of intermediate-high SS (>22). Subgroup analysis indicated that the relation between hs-CRP and SS was also consistent in acute coronary syndrome and its subtypes. Although elevated hs-CRP was positively associated with increased rates of MACEs (11.0% versus 12.1% versus 14.3%, p=0.006), death (1.0% versus 1.3% versus 3.0%, p<0.001), and revascularization (8.6% versus 10.4% versus 10.0%, p=0.032), it did not show any prognostic effect for adverse outcomes in multivariate regression analyses (all adjusted p> 0.05). While SS>22 remained independently predictive of MACEs and revascularization after adjusting confounders, the risks of which were increased by 56% and 68%, respectively. CONCLUSION Serum hs-CRP could be a useful biomarker for indicating CAD severity and could aid in risk stratification.
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Affiliation(s)
- Yue Liu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Si-da Jia
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yi Yao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xiao-Fang Tang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Na Xu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Lin Jiang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zhan Gao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jue Chen
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yue-Jin Yang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Run-Lin Gao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Bo Xu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
| | - Jin-Qing Yuan
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
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41
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Oliveira SHP, Brito VGB, Frasnelli SCT, Ribeiro BDS, Ferreira MN, Queiroz DP, Beltan CT, Lara VS, Santos CF. Aliskiren Attenuates the Inflammatory Response and Wound Healing Process in Diabetic Mice With Periodontal Disease. Front Pharmacol 2019; 10:708. [PMID: 31333451 PMCID: PMC6620569 DOI: 10.3389/fphar.2019.00708] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 05/31/2019] [Indexed: 01/08/2023] Open
Abstract
The aim of this study was to characterize the role of local RAS (renin–angiotensin system) in the inflammatory response of normal (N) and diabetic (D) mice with periodontal disease (PD). Diabetes Mellitus (DM) was induced by peritoneal injection of streptozotocin in Balb/c mice. PD was induced by ligature around the first molar in both N and D, irrespective of whether they were treated with aliskiren (50 mg/kg, Alisk). Mandibles were harvested for histomorphometric analyses, and gingival tissue (GT) was collected to evaluate gene expression and extracellular matrix components (ECM). Immunohistochemical (IHC) analyses were used to localize RAS in GT. The production of C-reactive protein (CRP), IL-1β, CXCL2, and CCL8 was evaluated by enzyme-linked immunosorbent assay (ELISA). Renin was found to exacerbate the inflammation and periodontal bone loss at 14 days after PD, and Alisk inhibited this process in GT of N and D. PD increased CRP, CXCL2, CCL8, and IL-1β production in both animals. Alisk could inhibit CRP, CXCL2, and CCL8 primarily in D animals. However, only CCL8 was decreased in N animals after Alisk pretreatment. PD enhanced expression and production of AGT, ACE, AT1R, and AT2R in both N and D. AT1R expression was higher in D with PD, and AT2R expression was higher in N with PD. ACE2 and receptor Mas (MasR) expression and production was elevated in the control group of both animals. PD inhibited ACE2 in N but not in D. MasR expression was unaffected in both N and D with PD. Alisk reduced expression and production of all RAS components in GT of both animals, except for ACE2 in N. RAS staining was observed in all layers of epithelium, basal cell layer, and lamina propria and was higher in N with PD. Col1a1, Col1a2, Col3a1, and fibronectin (Fn1) were increased in both animals with PD. Alisk inhibited Col1a1 and Fn in both animals, Col1a2 was decreased only in D, while levels of Col3a1 remained unchanged in all animal groups. In conclusion, these data demonstrated the presence and functional role of local RAS in GT, exacerbating the inflammatory response, periodontal bone loss, and wound healing processes in both N and D animal groups. In addition, Alisk was able to significantly reduce gingival inflammation, excessive wound healing processes, and periodontal bone loss.
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Affiliation(s)
- Sandra Helena Penha Oliveira
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil.,Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Victor Gustavo Balera Brito
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil.,Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Sabrina Cruz Tfaile Frasnelli
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Bianca da Silva Ribeiro
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Milena Nunes Ferreira
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Dayane Priscilla Queiroz
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil.,Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Carluci Taís Beltan
- Department of Basic Sciences, School of Dentistry of Araçatuba, São Paulo State University (UNESP), São Paulo, Brazil
| | - Vanessa Soares Lara
- Department of Stomatology, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
| | - Carlos Ferreira Santos
- Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
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42
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Involvement of circulating inflammatory factors in prognosis and risk of cardiovascular disease. J Mol Cell Cardiol 2019; 132:110-119. [DOI: 10.1016/j.yjmcc.2019.05.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/09/2019] [Accepted: 05/12/2019] [Indexed: 12/11/2022]
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Wang W, Ren D, Wang CS, Li T, Yao HC, Ma SJ. Prognostic efficacy of high-sensitivity C-reactive protein to albumin ratio in patients with acute coronary syndrome. Biomark Med 2019; 13:811-820. [PMID: 31144514 DOI: 10.2217/bmm-2018-0346] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The present study aimed to examine the correlation between high-sensitivity CRP to albumin ratio (CAR) and in-hospital and short-term major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). Materials & methods: We analyzed 652 consecutive patients who had been hospitalized for ACS. The MACEs were defined as cardiogenic shock, reinfarction, acute heart failure and all-cause death. Results: The incidence rate of MACEs was significantly higher in the high CAR (≥0.114) group than in the low CAR (<0.114) group. Multivariate analysis revealed that CAR, hs-CRP and albumin were independent predictors for increased risk for MACEs. Conclusion: The CAR was independently correlated with in-hospital and short-term MACEs and can be used for risk stratification in patients with ACS.
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Affiliation(s)
- Wei Wang
- Department of Cardiology, Liaocheng People's Hospital Affiliated to Shandong University & Clinical School of Taishan Medical University, Liaocheng 252000, People's Republic of China
| | - Dong Ren
- Department of Cardiology, Liaocheng People's Hospital Affiliated to Shandong University & Clinical School of Taishan Medical University, Liaocheng 252000, People's Republic of China
| | - Chun-Song Wang
- Department of Cardiology, Liaocheng People's Hospital Affiliated to Shandong University & Clinical School of Taishan Medical University, Liaocheng 252000, People's Republic of China
| | - Tai Li
- Department of Cardiology, The Third People's Hospital of Liaocheng, Liaocheng 252000, People's Republic of China
| | - Heng-Chen Yao
- Department of Cardiology, Liaocheng People's Hospital Affiliated to Shandong University & Clinical School of Taishan Medical University, Liaocheng 252000, People's Republic of China
| | - Sheng-Jun Ma
- Department of Cardiac Surgery, Liaocheng People's Hospital Affiliated to Shandong University & Clinical School of Taishan Medical University, Liaocheng 252000, People's Republic of China
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44
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Boncler M, Wu Y, Watala C. The Multiple Faces of C-Reactive Protein-Physiological and Pathophysiological Implications in Cardiovascular Disease. Molecules 2019; 24:E2062. [PMID: 31151201 PMCID: PMC6600390 DOI: 10.3390/molecules24112062] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 05/24/2019] [Accepted: 05/29/2019] [Indexed: 01/08/2023] Open
Abstract
C-reactive protein (CRP) is an intriguing protein which plays a variety of roles in either physiological or pathophysiological states. For years it has been regarded merely as a useful biomarker of infection, tissue injury and inflammation, and it was only in the early 80s that the modified isoforms (mCRP) of native CRP (nCRP) appeared. It soon became clear that the roles of native CRP should be clearly discriminated from those of the modified form and so the impacts of both isoforms were divided to a certain degree between physiological and pathophysiological states. For decades, CRP has been regarded only as a hallmark of inflammation; however, it has since been recognised as a significant predictor of future episodes of cardiovascular disease, independent of other risk factors. The existence of modified CRP isoforms and their possible relevance to various pathophysiological conditions, suggested over thirty years ago, has prompted the search for structural and functional dissimilarities between the pentameric nCRP and monomeric mCRP isoforms. New attempts to identify the possible relevance between the diversity of structures and their opposing functions have initiated a new era of research on C-reactive protein. This review discusses the biochemical aspects of CRP physiology, emphasizing the supposed relevance between the structural biology of CRP isoforms and their differentiated physiological and pathophysiological roles.
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Affiliation(s)
- Magdalena Boncler
- Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, 92-215 Lodz, Poland.
| | - Yi Wu
- MOE Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University, West Yanta Road, Xi'an 710061, China.
| | - Cezary Watala
- Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, 92-215 Lodz, Poland.
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45
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Kosmas CE, Silverio D, Sourlas A, Montan PD, Guzman E, Garcia MJ. Anti-inflammatory therapy for cardiovascular disease. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:147. [PMID: 31157268 DOI: 10.21037/atm.2019.02.34] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Chronic subclinical inflammation is a central process in the pathogenesis of cardiovascular disease (CVD) and it has been linked with both the initiation and progression of atherosclerosis. Several pro-inflammatory cytokines, such as the C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) have been described as independent risk factors for coronary heart disease and promoters of atherogenesis. Thus, extensive research is being conducted to assess the role of anti-inflammatory therapy in the primary and secondary prevention of CVD. Our review aims to provide the clinical and scientific data pertaining to the effects of different anti-inflammatory agents administered in patients with CVD.
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Affiliation(s)
| | - Delia Silverio
- Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA
| | | | - Peter D Montan
- Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA
| | - Eliscer Guzman
- Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Mario J Garcia
- Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
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46
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Zhu M, Lin J, Wang C, Yang M, Lv H, Yang M, Xu B, Chen X, Jiang J. The relationship among angiotensinogen genes polymorphisms and hs-CRP and coronary artery disease. J Clin Lab Anal 2019; 33:e22881. [PMID: 30912862 PMCID: PMC6595333 DOI: 10.1002/jcla.22881] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 02/11/2019] [Accepted: 02/21/2019] [Indexed: 02/02/2023] Open
Abstract
OBJECTIVE To assess the association of gene polymorphisms of angiotensinogen (AGT), the key factor in rennin-angiotensin-aldosterone system (RAAS), with high-sensitivity C-reactive protein (hs-CRP) and coronary artery disease (CAD). METHODS The current study recruited the patients who were hospitalized and assessed by coronary angiography for suspected CAD. The patients with documented CAD served as CAD group (n = 492) while the patients without documented CAD (n = 87) served as control group. We compared laboratory data and CAD risk factors between the two groups. Furthermore, we analyzed the association of AGT M235T, G217A, G152A, G-6A, A-20C genotypes with coronary artery stenosis and in-stent restenosis. RESULTS There were significantly differences between two patient groups in sex, smoking history, diabetes mellitus, carotid atherosclerosis, lower limb arteriosclerosis, hs-CRP, blood glucose, and the level of high-density lipoprotein (HDL; P < 0.05). In CAD group, hs-CRP levels increased with increasing number of coronary artery branches (1, 2, or ≥3; P < 0.01), and Gensini integral was positively correlated with hs-CRP levels (r = 0.361, P < 0.01). Frequencies of genotype and allele distribution in individual angiotensinogen loci (M235T, G217A, G152A, G-6A, A-20C) did not differ in two patient groups. Following stratification of patients according to hs-CRP levels (<1 mg/L, 1-3 mg/L, and >3 mg/L), the distribution frequency of allele M235T was statistically different among the groups (P < 0.05). CONCLUSION In CAD patients, M235T among several AGT gene polymorphisms is associated with elevated hs-CRP levels with AGT C allele as the significant factor for patients with hs-CRP level of more than 1 mg/L.
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Affiliation(s)
- Min Zhu
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Enze Medical Research Center, Taizhou, China
| | - Jiangbo Lin
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China
| | - Chen Wang
- Enze Medical Research Center, Taizhou, China
| | - Minjun Yang
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China
| | - Haiyan Lv
- Enze Medical Research Center, Taizhou, China
| | - Mengqi Yang
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China
| | - Baohui Xu
- Department of Surgery, Stanford University School of Medicine, Stanford, USA
| | - Xiaofeng Chen
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Enze Medical Research Center, Taizhou, China.,Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China
| | - Jianjun Jiang
- Laboratory of Cardiovascular Disease, Taizhou Hospital, Wenzhou Medical University, Taizhou, China.,Department of Cardiology, Taizhou Hospital, Wenzhou Medical University, Taizhou, China
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47
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Li J, Sun M, Ye J, Li Y, Jin R, Zheng H, Liang F. The Mechanism of Acupuncture in Treating Essential Hypertension: A Narrative Review. Int J Hypertens 2019; 2019:8676490. [PMID: 30984420 PMCID: PMC6431462 DOI: 10.1155/2019/8676490] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 02/14/2019] [Indexed: 01/13/2023] Open
Abstract
Essential hypertension has a high incidence worldwide, and patients with essential hypertension endure a lifetime of medication, leading to a heavy economic burden on the patient's family and causing serious impacts on the patient's quality of life. Much evidence has demonstrated that acupuncture as an adjunctive therapy can lower blood pressure in patients with hypertension, but the mechanism of its action is unclear. This article reviews the research from 2000 to 2018 regarding the mechanism of acupuncture for hypertension, and we summarize the current knowledge about using acupuncture for hypertension. We found that the mechanism whereby acupuncture lowers blood pressure is related to the regulation of renin-angiotensin-aldosterone system, vascular endothelium, oxidative stress, neuroendocrine system, and so on. Besides, there may be cross-talk between multiple systems and multiple targets. We also investigate the influence factors of acupuncture for hypertension. These results may provide evidence and research ideas for the treatment of hypertension via acupuncture.
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Affiliation(s)
- Juan Li
- College of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Mingsheng Sun
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Jing Ye
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Yuxi Li
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Rongjiang Jin
- College of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Hui Zheng
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Fanrong Liang
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
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48
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Salmenkari H, Laitinen A, Forsgård RA, Holappa M, Lindén J, Pasanen L, Korhonen M, Korpela R, Nystedt J. The use of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis: a pre-clinical study. Cytotherapy 2019; 21:175-188. [PMID: 30611671 DOI: 10.1016/j.jcyt.2018.11.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 10/04/2018] [Accepted: 11/13/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various pre-clinical and clinical IBD studies is also challenging due to a large variation in study designs. METHODS In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryopreserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1β and tumor necrosis factor (TNF)α concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1β and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis. RESULTS Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1β protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon. CONCLUSIONS In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.
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Affiliation(s)
- Hanne Salmenkari
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Anita Laitinen
- Advanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland
| | - Richard A Forsgård
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mervi Holappa
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jere Lindén
- Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Lauri Pasanen
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Matti Korhonen
- Advanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland
| | - Riitta Korpela
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Johanna Nystedt
- Advanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland.
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49
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Deciphering Endothelial Dysfunction in the HIV-Infected Population. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1134:193-215. [PMID: 30919339 DOI: 10.1007/978-3-030-12668-1_11] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Cardiovascular disease (CVD), as a possible consequence of endothelial dysfunction, is prevalent among HIV-infected patients despite successful administration of antiretroviral drugs. This warrants the routine clinical assessment of endothelial function in HIV-positive patients to circumvent potential CVD events. Several different non-invasive strategies have been employed to assess endothelial function in clinical research studies yielding inconsistencies among these reports. This review summarises the different techniques used for assessing endothelial function, with a focus on proposed blood-based biomarkers, such as endothelial leukocyte adhesion molecule-1 (E-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), TNF-α, interleukin 6 (IL6) and soluble thrombomodulin (sTM). The identification of suitable blood-based biomarkers, especially those that can be measured using a point-of-care device, would be more applicable in under-resourced countries where the prevalence of HIV is high.
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50
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Su H, Pei Y, Tian C, Zhang Q, Liu L, Meng G, Yao Z, Wu H, Xia Y, Bao X, Gu Y, Sun S, Wang X, Zhou M, Jia Q, Song K, Sun Z, Niu K. Relationship between high-sensitivity C-reactive protein and subclinical carotid atherosclerosis stratified by glucose metabolic status in Chinese adults. Clin Cardiol 2018; 42:39-46. [PMID: 30318598 DOI: 10.1002/clc.23095] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 10/10/2018] [Accepted: 10/11/2018] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Atherosclerosis is an inflammatory disease. Many studies demonstrated that hyperglycemia is not only increased inflammatory response, but also is a cause of atherosclerosis, implying that glucose metabolic status may be an important stratification factor when analyzing the relationship between inflammatory levels and subclinical carotid atherosclerosis. The aim of the present study is to assess the relationship between inflammatory levels and subclinical carotid atherosclerosis, stratified by different glucose metabolic status in a general population. METHODS An assessment was performed in 7975 participants living in Tianjin, China. In the present study, we examined subclinical carotid atherosclerosis, as defined by increased carotid intima-media thickness [IMT] and plaques. Measurements were performed using a carotid artery B-mode ultrasound system. The glucose metabolic status was defined by the criteria of the American Diabetes Association, and high-sensitivity C-reactive protein (hs-CRP) as an inflammatory indicator, was measured by immunoturbidimetric assay. Multiple logistic models were used to assess a stratified relationship between hs-CRP levels and subclinical carotid atherosclerosis. Strata were defined according to glucose metabolic status. RESULTS The prevalence of increased IMT and plaques were 27.3% and 21.3%, respectively. The adjusted odds ratios (95% confidence interval) for IMT across hs-CRP quartiles were as follows: 1.00 (reference), 1.10(0.88-1.38), 1.08(0.86-1.35) and 1.32(1.06-1.66) in blood glucose-normal subjects; 1.00 (reference), 1.33(0.92-1.91), 1.33(0.93-1.91), and 1.59(1.10-2.30) in prediabetic subjects; 1.00 (reference), 0.94(0.54-1.62), 1.17(0.65-2.12) and 0.98(0.55-1.76) in diabetic subjects, respectively. Similar results were observed for plaques. CONCLUSIONS Our results suggest that inflammatory levels are differently related to subclinical carotid atherosclerosis by the different glucose metabolic status.
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Affiliation(s)
- Haiyan Su
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Yinghua Pei
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Chunling Tian
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Zhanxin Yao
- Tianjin Institute of Environmental & Operational Medicine, Tianjin, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yang Xia
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xue Bao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhong Sun
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Kaijun Niu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
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