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Chen L, Jiang Y. Association Study of MTHFR C677T Polymorphism With Homocysteine Level and Coronary Heart Disease in Elderly Patients. Cardiol Res Pract 2025; 2025:6246458. [PMID: 40123720 PMCID: PMC11930381 DOI: 10.1155/crp/6246458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 02/27/2025] [Indexed: 03/25/2025] Open
Abstract
Objective: To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and coronary heart disease (CHD) in the elderly patients living in the coastal area of eastern Zhejiang Province in China. Methods: From September 2021 to May 2022, 163 elderly patients (male ≥ 55 years old, female ≥ 65 years old) admitted to the cardiology department in the Ningbo Lihuili Hospital were collected. Among these patients, 90 patients were diagnosed with CHD (CHD group) and 79 patients did not have CHD (control group). The homocysteine (Hcy) level was measured by the blood biochemical test, and the MTHFR genotype was detected by the PCR fluorescence probe method. Results: Compared with the control group, the CHD group showed a significantly higher distribution frequency of TT genotype (X 2 = 5.137, p < 0.05) and a lower frequency of CC genotype (X 2 = 6.560, p < 0.05), indicating that elderly people with MTHFR677 TT genotype are more likely to have CHD. In addition, the Hcy level of TT genotype in the CHD group and the control group were both obviously higher than that of CT genotype and CC genotype (p < 0.05). Finally, the univariate and multivariate logistic regression analyses showed that gender, hypertension, diabetes, and MTHFR677 TT genotype were independent risk factors for CHD (p < 0.05). Conclusion: MTHFR C677T mutation is significantly associated with the serum Hcy, and is an important genetic risk for CHD development in the elderly people living in the coastal area of eastern Zhejiang province, China.
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Affiliation(s)
- Li Chen
- Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315040, China
| | - Yi Jiang
- Ningbo Medical Center, Lihuili Hospital, Ningbo University, Ningbo, Zhejiang 315040, China
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Chen Y, Shan S, Xue Q, Ren Y, Wu Q, Chen J, Yang K, Cao J. Sirtuin1 mitigates hypoxia-induced cardiomyocyte apoptosis in myocardial infarction via PHD3/HIF-1α. Mol Med 2025; 31:100. [PMID: 40087582 PMCID: PMC11909899 DOI: 10.1186/s10020-025-01155-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: 12/20/2024] [Accepted: 03/05/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Acute myocardial infarction (AMI) is a leading cause of mortality, characterized by myocardial ischemia that induces cardiomyocyte apoptosis and subsequent cardiac dysfunction. Sirtuin 1 (Sirt1) has emerged as a key regulator of cell survival and apoptosis, particularly under hypoxic conditions. METHODS An AMI animal model was established via ligation of the left anterior descending (LAD) coronary artery. Gene expression in the infarcted region was evaluated at various time points. Sirt1 overexpression and control lentivirus were administered to the peri-infarct region of mice heart. After LAD ligation, assessment on myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were performed. In vitro, primary mouse cardiomyocytes subjected to hypoxia were analyzed for gene expression, while interactions among Sirt1, Phd3, and Hif-1α were explored using diverse treatment approaches. RESULTS A significant reduction in Sirt1 and Phd3 expression, along with an increase in Hif-1α and cleaved caspase-3, was observed in a time-dependent manner post-myocardial infarction (MI). In vitro findings revealed that hypoxia decreased nuclear Sirt1 and cytoplasmic Phd3 levels while promoting a time-dependent increase in Hif-1α and cleaved caspase-3. Furthermore, Sirt1 overexpression enhanced Phd3 expression in cardiomyocytes, suppressed Hif-1α and cleaved caspase-3 levels, and alleviated hypoxia-induced cardiomyocyte apoptosis. Notably, knockdown of Phd3 negated Sirt1's inhibitory effect on Hif-1α, whereas Hif-1α knockdown promoted Sirt1 expression. Sirt1 overexpression reduced infarct size, decreased cardiomyocyte apoptosis, and improved cardiac function. CONCLUSIONS Sirt1 effectively reduces cardiomyocyte apoptosis and myocardial infarction size while enhancing cardiac function post-MI, primarily through the Phd3/Hif-1α signaling pathway.
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Affiliation(s)
- Yafen Chen
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shuyao Shan
- Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China
| | - Qiqi Xue
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China
| | - Yan Ren
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China
| | - Qihong Wu
- Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China
| | - Jiawei Chen
- Department of Cardiology, Shanghai Ninth People'S Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
| | - Ke Yang
- Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China.
| | - Jiumei Cao
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People's Republic of China.
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Holme S, Richardson SM, Bella J, Pinali C. Hydrogels for Cardiac Tissue Regeneration: Current and Future Developments. Int J Mol Sci 2025; 26:2309. [PMID: 40076929 PMCID: PMC11900105 DOI: 10.3390/ijms26052309] [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: 01/15/2025] [Revised: 02/23/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
Myocardial infarction remains a leading cause of death worldwide due to the heart's limited regenerative capability and the current lack of viable therapeutic solutions. Therefore, there is an urgent need to develop effective treatment options to restore cardiac function after a heart attack. Stem cell-derived cardiac cells have been extensively utilised in cardiac tissue regeneration studies. However, the use of Matrigel as a substrate for the culture and maturation of these cells has been a major limitation for the translation of this research into clinical application. Hydrogels are emerging as a promising system to overcome this problem. They are biocompatible and can provide stem cells with a supportive scaffold that mimics the extracellular matrix, which is essential for repairing damaged tissue in the myocardium after an infarction. Thus, hydrogels provide an alternative and reproducible option in addressing myocardial infarction due to their unique potential therapeutic benefits. This review explores the different types of natural and synthetic polymers used to create hydrogels and their various delivery methods, the most common being via injection and cardiac patches and other applications such as bioprinting. Many challenges remain before hydrogels can be used in a clinical setting, but they hold great promise for the future of cardiac tissue regeneration.
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Affiliation(s)
- Sonja Holme
- Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; (S.H.); (S.M.R.)
| | - Stephen M. Richardson
- Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; (S.H.); (S.M.R.)
| | - Jordi Bella
- Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK; (S.H.); (S.M.R.)
| | - Christian Pinali
- Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK
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Zhang L, Zhou J. Zebrafish: A smart tool for heart disease research. JOURNAL OF FISH BIOLOGY 2024; 105:1487-1500. [PMID: 37824489 DOI: 10.1111/jfb.15585] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/07/2023] [Accepted: 10/09/2023] [Indexed: 10/14/2023]
Abstract
The increasing prevalence of heart disease poses a significant threat to human survival and safety. However, the current treatments available for heart disease are quite limited. Therefore, it is important to utilize suitable animal models that can accurately simulate the physiological characteristics of heart disease. This would help improve our understanding of this disease and aid in the development of new treatment methods and drugs. Zebrafish heart not only exhibits similarities to mammalian hearts, but they also share ~70% of homologous genes with humans. Utilizing zebrafish as an alternative to expensive and time-consuming mammalian models offers numerous advantages. Zebrafish models can be easily established and maintained, and compound screening and genetic methods allow for the development of various economical and easily controlled zebrafish and zebrafish embryonic heart disease models in a short period of time. Consequently, zebrafish have become a powerful tool for exploring the pathological mechanisms of heart disease and identifying new effective genes. In this review, we summarize recent studies on different zebrafish models of heart disease. We also describe the techniques and protocols used to develop zebrafish models of myocardial infarction, heart failure, and congenital heart disease, including surgical procedures, forward and reverse genetics, and drug and combination screening. This review aims to promote the utilization of zebrafish models in investigating diverse pathological mechanisms of heart disease, enhancing our knowledge and comprehension of heart disease, and offering novel insights and objectives for exploring the prevention and treatment of heart disease.
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Affiliation(s)
- Lantian Zhang
- Education Branch, Chongqing Publishing Group, Chongqing, China
| | - Jinrun Zhou
- Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, China
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Jasiewicz NE, Mei K, Oh HM, Bonacquisti EE, Chaudhari A, Byrum C, Jensen BC, Nguyen J. In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention. Bioeng Transl Med 2024; 9:e10697. [PMID: 39545082 PMCID: PMC11558206 DOI: 10.1002/btm2.10697] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/10/2024] [Accepted: 06/29/2024] [Indexed: 11/17/2024] Open
Abstract
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate-buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.
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Affiliation(s)
- Natalie E. Jasiewicz
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Kuo‐Ching Mei
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Hannah M. Oh
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Emily E. Bonacquisti
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Ameya Chaudhari
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Camryn Byrum
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
| | - Brian C. Jensen
- McAllister Heart Institute, University of North CarolinaChapel HillNorth CarolinaUSA
- Division of Cardiology, Department of MedicineUniversity of North CarolinaChapel HillNorth CarolinaUSA
| | - Juliane Nguyen
- Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of Pharmacy, University of North CarolinaChapel HillNorth CarolinaUSA
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Wang FD, Ding Y, Zhou JH, Zhou E, Zhang TT, Fan YQ, He Q, Zhang ZQ, Mao CY, Zhang JF, Zhou J. Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation. World J Stem Cells 2024; 16:873-895. [PMID: 39493825 PMCID: PMC11525649 DOI: 10.4252/wjsc.v16.i10.873] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 08/21/2024] [Accepted: 09/27/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Myocardial ischemia-reperfusion injury (MIRI) poses a prevalent challenge in current reperfusion therapies, with an absence of efficacious interventions to address the underlying causes. AIM To investigate whether the extracellular vesicles (EVs) secreted by adipose mesenchymal stem cells (ADSCs) derived from subcutaneous inguinal adipose tissue (IAT) under γ-aminobutyric acid (GABA) induction (GABA-EVsIAT) demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms. METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA. We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays. The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds. To explore the functional RNA diversity between EVsIAT and GABA-EVsIAT, we employed microRNA (miR) sequencing. Through a dual-luciferase reporter assay, we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein (TXNIP). Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction. RESULTS Our study demonstrates that, under the influence of GABA, ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs. Consequently, this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention, ultimately resulting in myocardial protection. On a molecular mechanism level, EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes. CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs, thereby regulating the expression of TXNIP. The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.
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Affiliation(s)
- Feng-Dan Wang
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Yi Ding
- Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jian-Hong Zhou
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - En Zhou
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Tian-Tian Zhang
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Yu-Qi Fan
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Qing He
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Zong-Qi Zhang
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Cheng-Yu Mao
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jun-Feng Zhang
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jing Zhou
- Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
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Nelson VL, Eadie AL, Perez L, Madhu M, Platt M, Mercer A, Pulinilkunnil T, Kienesberger P, Simpson JA, Brunt KR. Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes. Biomolecules 2024; 14:1299. [PMID: 39456232 PMCID: PMC11506509 DOI: 10.3390/biom14101299] [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: 09/10/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 10/28/2024] Open
Abstract
Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)-a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.
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Affiliation(s)
- Victoria L. Nelson
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
| | - Ashley L. Eadie
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
| | - Lester Perez
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
| | - Malav Madhu
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
| | - Mathew Platt
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Angella Mercer
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
- Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Thomas Pulinilkunnil
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
- Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Petra Kienesberger
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
- Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Jeremy A. Simpson
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
| | - Keith R. Brunt
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Dalhousie Medicine New Brunswick, Faculty of Medicine, Dalhousie University, Saint John, NB E2L 4L5, Canada
- IMPART Investigator Team Canada, Saint John, NB E2L 4L5, Canada
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Dragomir L, Marina V, Anghele AD, Anghele M, Moscu CA. The Prevalence of ST-Segment Elevation Myocardial Infarction in Patients Presenting in the Emergency Service of Galati Hospital from 2015 to 2019. Clin Pract 2024; 14:1417-1429. [PMID: 39051308 PMCID: PMC11270415 DOI: 10.3390/clinpract14040114] [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: 06/17/2024] [Revised: 07/05/2024] [Accepted: 07/11/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND AND OBJECTIVES The purpose of this study is to determine the prevalence of cardiovascular emergencies and the relationships between these emergencies and the personal medical histories of patients. MATERIALS AND METHODS This study is retrospective, observational, and longitudinal, spanning five years from 1 January 2015 to 31 December 2019. Descriptive elements were observed and recorded to conduct statistical analysis on the cardiovascular characteristics of 723 patients transported by air and treated at the Emergency County Hospital of Galati, Romania. RESULTS Cardiovascular disease is a complex condition that often originates in the heart and presents with a variety of symptoms. Deaths related to cardiovascular diseases outnumber cancer-related deaths in both men and women worldwide. The one-year mortality rate for patients admitted to the hospital with acute pulmonary edema can be as high as 40%. Coronary heart disease is the leading cause of death and disability in the Western world and globally. CONCLUSIONS The highest prevalence of cardiovascular diseases was noted in 2016, particularly among elderly men, who appear to be more affected by these conditions, while liver disease was minimal. In our study, the most prevalent cardiovascular disease was ST-elevation myocardial infarction. Gender plays a role in the risk of cardiovascular emergencies, with men being at a higher risk of developing life-threatening conditions. Additionally, there is a linear increase in risk with age for developing these pathologies.
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Affiliation(s)
- Liliana Dragomir
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, Romania; (L.D.); (A.-D.A.); (C.-A.M.)
| | - Virginia Marina
- Medical Department of Occupational Health, Facultatea de Medicina si Farmacie, “Dunarea de Jos” University, 800008 Galati, Romania
| | - Aurelian-Dumitrache Anghele
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, Romania; (L.D.); (A.-D.A.); (C.-A.M.)
| | - Mihaela Anghele
- Clinical-Medical Department, Faculty of Medicine and Pharmacy, Dunărea de Jos University of Galati, 800201 Galati, Romania;
| | - Cosmina-Alina Moscu
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University of Galati, 800008 Galati, Romania; (L.D.); (A.-D.A.); (C.-A.M.)
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von Bibra C, Hinkel R. Non-human primate studies for cardiomyocyte transplantation-ready for translation? Front Pharmacol 2024; 15:1408679. [PMID: 38962314 PMCID: PMC11221829 DOI: 10.3389/fphar.2024.1408679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 05/21/2024] [Indexed: 07/05/2024] Open
Abstract
Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation.
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Affiliation(s)
- Constantin von Bibra
- Institute for Animal Hygiene, Animal Welfare and Farm Animal Behavior, Stiftung Tieraerztliche Hochschule Hannover, University of Veterinary Medicine, Hanover, Germany
- Laboratory Animal Science Unit, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany
- DZHK (German Centre of Cardiovascular Research), Partner Site Lower Saxony, Goettingen, Germany
| | - Rabea Hinkel
- Institute for Animal Hygiene, Animal Welfare and Farm Animal Behavior, Stiftung Tieraerztliche Hochschule Hannover, University of Veterinary Medicine, Hanover, Germany
- Laboratory Animal Science Unit, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany
- DZHK (German Centre of Cardiovascular Research), Partner Site Lower Saxony, Goettingen, Germany
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Yuan C, Yang H, Lan W, Yang J, Tang Y. Nicotinamide ribose ameliorates myocardial ischemia/reperfusion injury by regulating autophagy and regulating oxidative stress. Exp Ther Med 2024; 27:187. [PMID: 38533432 PMCID: PMC10964731 DOI: 10.3892/etm.2024.12475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 02/08/2024] [Indexed: 03/28/2024] Open
Abstract
Nicotinamide riboside (NR) has been reported to play a protective role in myocardial ischemia-reperfusion (I/R) injury when used in association with other drugs; however, the individual effect of NR is unknown. In the present study Evan's blue/triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, echocardiography, western blotting, reverse transcription-quantitative PCR, and the detection of myocardial injury-associated markers and oxidative stress metabolites were used to explore the ability of NR to alleviate cardiac I/R injury and the relevant mechanisms of action. In a mouse model of I/R injury, dietary supplementation with NR reduced the area of myocardial ischemic infarction, alleviated pathological myocardial changes, decreased inflammatory cell infiltration and attenuated the levels of mitochondrial reactive oxygen species (ROS) and creatine kinase myocardial band (CK-MB). In addition, echocardiography suggested that NR alleviated the functional damage of the myocardium caused by I/R injury. In H9c2 cells, NR pretreatment reduced the levels of lactate dehydrogenase, CK-MB, malondialdehyde, superoxide dismutase and ROS, and reduced cell mortality after the induction of hypoxia/reoxygenation (H/R) injury. In addition, the results indicated NR activated sirt 1 via the upregulation of nicotinamide adenine dinucleotide (NAD+) and protected the cells against autophagy. The sirt 1 inhibitor EX527 significantly attenuated the ability of NR to inhibit autophagy, but had no significant effect on the ROS content of the H9c2 cells. In summary, the present study suggests that NR protects against autophagy by increasing the NAD+ content in the body via the sirt 1 pathway, although the sirt 1 pathway does not affect oxidative stress.
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Affiliation(s)
- Chen Yuan
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
- East China Institute of Digital Medical Engineering, Shangrao, Jiangxi 334100, P.R. China
| | - Heng Yang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
| | - Wanqi Lan
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
| | - Juesheng Yang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
| | - Yanhua Tang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China
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11
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Slack RJ, McGain F, Cox N, French C, Cheng V, Stub D, Zakhem B, Dade F, Bloom JE, Chan W, Yang Y. Structured Weaning From the Impella Left Ventricular Micro-Axial Pump in Acute Myocardial Infarction With Cardiogenic Shock and Protected Percutaneous Coronary Intervention: Experience From a Non-Cardiac Surgical Centre. Heart Lung Circ 2024; 33:460-469. [PMID: 38388259 DOI: 10.1016/j.hlc.2023.12.007] [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: 05/28/2023] [Revised: 09/08/2023] [Accepted: 12/10/2023] [Indexed: 02/24/2024]
Abstract
BACKGROUND The Impella (Abiomed, Danvers, MA, USA) temporary percutaneous left ventricular assist device is increasingly used as mechanical circulatory support in patients with acute myocardial infarction-cardiogenic shock (AMICS) or those undergoing high-risk protected percutaneous coronary intervention (PCI). The optimal weaning regimen remains to be defined. METHOD We implemented a structured weaning protocol in a series of 10 consecutive patients receiving Impella support for protected PCI or AMICS treated with PCI in a high volume non-cardiac surgery centre. Weaning after revascularisation was titrated to native heart recovery using both haemodynamic and echocardiographic parameters. RESULTS Ten patients (eight male, two female; aged 43-70 years) received Impella support for AMICS (80%) or protected PCI (20%). Cardiogenic shock was of Society for Cardiac Angiography & Interventions grade C-E of severity in 80%, and median left ventricular end-diastolic pressure was 31 mmHg. Protocol implementation allowed successful weaning in eight of 10 patients with a median support time of 29 hours (range, 4-48 hours). Explantation was associated with an increase in heart rate (81 vs 88 bpm; p=0.005), but no significant change in Cardiac Index (2.9 vs 2.9 L/min/m2), mean arterial pressure (79 vs 82 mmHg), vasopressor requirement (10% vs 10%), or serum lactate (1.0 vs 1.0). Median durations of intensive care and hospital stay were 3 and 6 days, respectively. At 30 days, the mortality rate was 20%, with median left ventricular ejection fraction of 40%. CONCLUSIONS A structured and dynamic weaning protocol for patients with AMICS and protected PCI supported by the Impella device is feasible in a non-cardiac surgery centre. Larger studies are needed to assess generalisability of such a weaning protocol.
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Affiliation(s)
- Ryan J Slack
- Intensive Care Unit Department, Western Health, Melbourne, Vic, Australia
| | - Forbes McGain
- Intensive Care Unit Department, Western Health, Melbourne, Vic, Australia
| | - Nicholas Cox
- Department of Cardiology, Western Health, Melbourne, Vic, Australia
| | - Craig French
- Intensive Care Unit Department, Western Health, Melbourne, Vic, Australia
| | - Victoria Cheng
- Department of Cardiology, Western Health, Melbourne, Vic, Australia
| | - Dion Stub
- Department of Cardiology, Western Health, Melbourne, Vic, Australia; Department of Cardiology, Alfred Hospital, Melbourne, Vic, Australia
| | - Brian Zakhem
- Department of Cardiology, Western Health, Melbourne, Vic, Australia
| | - Fabien Dade
- Intensive Care Unit Department, Western Health, Melbourne, Vic, Australia
| | - Jason E Bloom
- Department of Cardiology, Western Health, Melbourne, Vic, Australia; Department of Cardiology, Alfred Hospital, Melbourne, Vic, Australia
| | - William Chan
- Department of Cardiology, Western Health, Melbourne, Vic, Australia; Department of Cardiology, Alfred Hospital, Melbourne, Vic, Australia
| | - Yang Yang
- Intensive Care Unit Department, Western Health, Melbourne, Vic, Australia.
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12
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Jasiewicz NE, Mei KC, Oh HM, Bonacquisti EE, Chaudhari A, Byrum C, Jensen BC, Nguyen J. In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.14.585030. [PMID: 38559120 PMCID: PMC10980051 DOI: 10.1101/2024.03.14.585030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction, but their therapeutic efficacy is limited by inefficient accumulation at the target site. A non-invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here we show that EVs decorated with the next-generation of high-affinity heterodimerizing leucine zippers, termed high-affinity (HiA) Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ∼7-fold enhanced accumulation within the infarcted myocardium in mice after three days and continued to be retained up to day 21, surpassing the performance of unmodified EVs. After myocardial infarction in mice, high-affinity Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and PBS, respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. High-affinity Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for non-invasive vesicle delivery to the infarcted heart. Translational Impact Statement Therapeutic delivery to the heart remains inefficient and poses a bottleneck in modern drug delivery. Surgical application and intramyocardial injection of therapeutics carry high risks for most heart attack patients. To address these limitations, we have developed a non-invasive strategy for efficient cardiac accumulation of therapeutics using in situ crosslinking. Our approach achieves high cardiac deposition of therapeutics without invasive intramyocardial injections. Patients admitted with myocardial infarction typically receive intravenous access, which would allow painless administration of Zippersomes alongside standard of care.
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13
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Tang X, Zhou Y, Chen Z, Liu C, Wu Z, Zhou Y, Zhang F, Lu X, Tang L. Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies. J Cell Mol Med 2024; 28:e18175. [PMID: 38451044 PMCID: PMC10919158 DOI: 10.1111/jcmm.18175] [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: 09/28/2023] [Revised: 01/07/2024] [Accepted: 01/31/2024] [Indexed: 03/08/2024] Open
Abstract
The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.
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Affiliation(s)
- Xiaoqi Tang
- School of MedicineShaoxing UniversityZhejiangChina
| | - Yufei Zhou
- Department of CardiologyShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan UniversityShanghaiChina
| | - Zhuolin Chen
- Department of OrthopedicsShaoxing People's Hospital (Zhejiang University School of Medicine)ShaoxingChina
| | - Chunjiang Liu
- Department of General Surgery, Division of Vascular SurgeryShaoxing People's HospitalShaoxingChina
| | - Zhifeng Wu
- School of MedicineShaoxing UniversityZhejiangChina
| | - Yue Zhou
- Department of General Surgery, Division of Vascular SurgeryShaoxing People's HospitalShaoxingChina
| | - Fan Zhang
- School of MedicineShaoxing UniversityZhejiangChina
| | - Xuanyuan Lu
- Department of OrthopedicsShaoxing People's Hospital (Zhejiang University School of Medicine)ShaoxingChina
| | - Liming Tang
- Department of General Surgery, Division of Vascular SurgeryShaoxing People's HospitalShaoxingChina
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14
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Pallangyo A, Pyuza JJ, Nkya G, Amsi P, Andongolile A, Makata AM, Mremi A. Ventricular silent rupture leading to sudden death: Navigating diagnostic challenges in a resource-constraint setting. Clin Case Rep 2024; 12:e8439. [PMID: 38197060 PMCID: PMC10774542 DOI: 10.1002/ccr3.8439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 11/29/2023] [Accepted: 01/02/2024] [Indexed: 01/11/2024] Open
Abstract
Key Clinical Message Ventricular myocardial rupture is a rare complication of myocardial infarction. It occurs within hours to weeks after an infarction. Mortality is high. Antemortem diagnosis is a challenge in low-resource settings, leading to potential misdiagnosis. Abstract Left ventricular myocardial rupture is a potentially fatal yet common complication in acute myocardial infarction patients. Rupture can occur as early as hours after an infarction. However, rupture may also occur later in the first week in the setting of myocardial necrosis and neutrophilic infiltration. Patients may survive several days to weeks before rupture occurs, and cardiac tamponade may present subacutely with a slow or repetitive clinical course. Sudden death can be attributed to ventricular rupture, more commonly during this time frame. Myocardial rupture can also occur as a result of trauma, infections, or cancer. Mortality is exceedingly high if surgical intervention is delayed. In most patients, myocardial rupture manifests as a catastrophic event within days of a first, small, uncomplicated acute myocardial infarction. Acute onset of shortness of breath, chest pain, shock, diaphoresis, unexplained emesis, cool and clammy skin, and syncope may herald the onset of ventricular septal rupture after acute myocardial infarction. Sudden death from myocardial rupture during acute myocardial infarction in patients with no apparent previous symptoms of myocardial ischemia represents a challenge for medical examiners, law enforcement officers, and society as a whole. An autopsy is critical for establishing the cause of death. We present the case of a 54-year-old male whose body was found beside the road after a trivial quarrel a day before. Further medical information about the deceased was not available. The preliminary cause of death was presumed to be traumatic. No evidence of trauma was seen during the autopsy. Massive pericardial blood collection compressing the heart and concealed left ventricular myocardial rupture were noted. Histopathological examination of the heart demonstrated myocardial infarction with a tear associated with bleeding that was contained in the pericardial sac. We ruled cardiac tamponade as the cause of death due to an infarcted myocardial rupture. Antemortem diagnosis of myocardial rupture can be challenging in low-resource settings, leading to potential misdiagnosis and negative impacts such as community conflicts.
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Affiliation(s)
- Angela Pallangyo
- Department of PathologyKilimanjaro Christian Medical CentreMoshiTanzania
- Faculty of MedicineKilimanjaro Christian Medical University CollegeMoshiTanzania
| | - Jeremia J. Pyuza
- Department of PathologyKilimanjaro Christian Medical CentreMoshiTanzania
| | - Gilbert Nkya
- Department of PathologyKilimanjaro Christian Medical CentreMoshiTanzania
| | - Patrick Amsi
- Department of PathologyKilimanjaro Christian Medical CentreMoshiTanzania
- Faculty of MedicineKilimanjaro Christian Medical University CollegeMoshiTanzania
| | | | - Ahmed M. Makata
- Department of PathologyKampala International University in TanzaniaKampalaTanzania
| | - Alex Mremi
- Department of PathologyKilimanjaro Christian Medical CentreMoshiTanzania
- Faculty of MedicineKilimanjaro Christian Medical University CollegeMoshiTanzania
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15
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Amirzadeh Gougheri K, Ahmadi A, Ahmadabadi MG, Babajani A, Yazdanpanah G, Bahrami S, Hassani M, Niknejad H. Exosomal Cargo: Pro-angiogeneic, anti-inflammatory, and regenerative effects in ischemic and non-ischemic heart diseases - A comprehensive review. Biomed Pharmacother 2023; 168:115801. [PMID: 37918257 DOI: 10.1016/j.biopha.2023.115801] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 10/17/2023] [Accepted: 10/26/2023] [Indexed: 11/04/2023] Open
Abstract
Heart diseases are the primary cause of mortality and morbidity worldwide which inflict a heavy social and economic burden. Among heart diseases, most deaths are due to myocardial infarction (MI) or heart attack, which occurs when a decrement in blood flow to the heart causes injury to cardiac tissue. Despite several available diagnostic, therapeutic, and prognostic approaches, heart disease remains a significant concern. Exosomes are a kind of small extracellular vesicles released by different types of cells that play a part in intercellular communication by transferring bioactive molecules important in regenerative medicine. Many studies have reported the diagnostic, therapeutic, and prognostic role of exosomes in various heart diseases. Herein, we reviewed the roles of exosomes as new emerging agents in various types of heart diseases, including ischemic heart disease, cardiomyopathy, arrhythmia, and valvular disease, focusing on pathogenesis, therapeutic, diagnostic, and prognostic roles in different areas. We have also mentioned different routes of exosome delivery to target tissues, the effects of preconditioning and modification on exosome's capability, exosome production in compliance with good manufacturing practice (GMP), and their ongoing clinical applications in various medical contexts to shed light on possible clinical translation.
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Affiliation(s)
- Kowsar Amirzadeh Gougheri
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armin Ahmadi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amirhesam Babajani
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghasem Yazdanpanah
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, 1855 W. Taylor Street, MC 648, Chicago, IL 60612, USA
| | - Soheyl Bahrami
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA Research Center, Vienna, Austria
| | - Mohammad Hassani
- Department of Vascular and Endovascular Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Niknejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Wang Y, Liu Y, Fei A, Tan L. CircMACF1 alleviates myocardial fibrosis after acute myocardial infarction by suppressing cardiac fibroblast activation via the miR-16-5p/SMAD7 axis. Medicine (Baltimore) 2023; 102:e35119. [PMID: 37713818 PMCID: PMC10508453 DOI: 10.1097/md.0000000000035119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 08/17/2023] [Indexed: 09/17/2023] Open
Abstract
Circular RNAs (circRNAs) played a pivotal role in myocardial fibrosis after acute myocardial infarction (AMI). The activation of cardiac fibroblasts (CFs) and accumulation of extracellular matrix are the main characteristics of myocardial fibrosis. In our research, we aimed to elucidate the functional roles of circMACF1 in CF activation after AMI as well as the underlying mechanism. Human CFs were activated by TGF-β1 treatment. qPCR and western blotting were performed to investigate gene and protein expression. CCK-8 and transwell assays were carried out to measure cell proliferation, and migration. Immunofluorescence was used to investigate α-SMA level. The interaction between miR-16-5p and circMACF1 or SMAD7 was revealed by RIP or dual luciferase reporter gene assays. CircMACF1 and SMAD7 were repressed in AMI patients and CFs treated with TGF-β1, and miR-16-5p was increased. In addition, circMACF1 was resistant to RNase R and abundantly expressed in the cytoplasm. Overexpression of circMACF1 inhibited cell proliferation and migration and reduced the expression levels of fibrosis-related proteins, including Collagen I, Collagen III, and α-SMA. Furthermore, circMCAF1 could directly bind to miR-16-5p, and SMAD7 was a target gene of miR-16-5p. Knockdown of miR-16-5p suppressed the activation, proliferation, and migration of TGF-β1-treated CFs, but silencing circMACF1 or SMAD7 partially reversed this phenomenon. CircMACF1 attenuated the TGF-β1-induced activation, proliferation and migration of CFs via the miR-16-5p/SMAD7 signaling pathway, indicating that circMACF1 might be a new therapeutic target for AMI.
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Affiliation(s)
- Yonghong Wang
- Department of Cardiology, the Fourth Hospital of Changsha, Changsha, China
| | - Yanfei Liu
- Department of Cardiology, the Fourth Hospital of Changsha, Changsha, China
| | - Aike Fei
- Department of Cardiology, the Fourth Hospital of Changsha, Changsha, China
| | - Liming Tan
- Department of Cardiology, the Fourth Hospital of Changsha, Changsha, China
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17
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Zhakhina G, Gaipov A, Salustri A, Gusmanov A, Sakko Y, Yerdessov S, Bekbossynova M, Abbay A, Sarria-Santamera A, Akbilgic O. Incidence, mortality and disability-adjusted life years of acute myocardial infarction in Kazakhstan: data from unified national electronic healthcare system 2014-2019. Front Cardiovasc Med 2023; 10:1127320. [PMID: 37600059 PMCID: PMC10433224 DOI: 10.3389/fcvm.2023.1127320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 07/17/2023] [Indexed: 08/22/2023] Open
Abstract
Background Cardiovascular diseases contribute to premature mortality globally, resulting in substantial social and economic burdens. The Global Burden of Disease (GBD) Study reported that in 2019 alone, heart attack and strokes accounted for the deaths of 18.6 million individuals. Ischemic heart diseases, including acute myocardial infarction (AMI), accounted for 182 million disability-adjusted life years (DALYs) and it is leading cause of death worldwide. Aim The aim of this study is to present the burden of AMI in Kazakhstan and describe the outcome of hospitalized patients. Methods The data of 79,172 people admitted to hospital with ICD-10 diagnosis I21 between 2014 and 2019 was derived from the Unified National Electronic Health System and retrospectively analyzed. Results The majority of the cohort (53,285, 67%) were men, with an average age of 63 (±12) years, predominantly of Kazakh (38,057, 48%) and Russian (24,583, 31%) ethnicities. Hypertension was the most common comorbidity (61,972, 78%). In males, a sharp increase in incidence is present after 40 years, while for females, the morbidity increases gradually after 55. Throughout the observation period, all-cause mortality rose from 101 to 210 people per million population (PMP). In 2019, AMI account for 169,862 DALYs in Kazakhstan, with a significant proportion (79%) attributed to years of life lost due to premature death (YLDs). Approximately half of disease burden due to AMI (80,794 DALYs) was in age group 55-69 years. Although incidence is higher for men, they have better survival rates than women. In terms of revascularization procedures, coronary artery bypass grafting yielded higher survival rates compared to percutaneous coronary intervention (86.3% and 80.9% respectively) during the 5-year follow-up. Conclusion This research evaluated the burden and disability-adjusted life years of AMI in Kazakhstan, the largest Central Asian country. The results show that more effective disease management systems and preventive measures at earlier ages are needed.
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Affiliation(s)
- Gulnur Zhakhina
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Abduzhappar Gaipov
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
- Clinical Academic Department of Internal Medicine, CF “University Medical Center”, Astana, Kazakhstan
| | - Alessandro Salustri
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Arnur Gusmanov
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Yesbolat Sakko
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Sauran Yerdessov
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | | | - Anara Abbay
- Department of Medicine, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | | | - Oguz Akbilgic
- Cardiovascular Section, Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, United States
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18
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de Oliveira Laterza Ribeiro M, Hueb W, Rezende PC, Lima EG, Nomura CH, Rochitte CE, da Silva Selistre L, Boros GAB, Ramires JAF, Filho RK. Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease. Clin Imaging 2023; 101:142-149. [PMID: 37348160 DOI: 10.1016/j.clinimag.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/28/2023] [Accepted: 06/05/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Stress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). METHODS This is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. RESULTS Between May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. CONCLUSION AND RELEVANCE In this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.
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Affiliation(s)
| | - Whady Hueb
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
| | - Paulo Cury Rezende
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Eduardo Gomes Lima
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Cesar Higa Nomura
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Carlos Eduardo Rochitte
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | - Gustavo André Boeing Boros
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Jose Antonio Franchini Ramires
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Roberto Kalil Filho
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
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19
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Vasudevan E, Anton MC, Shanthi B, Sridevi C, Sumathi K, Nivethini N. Significance of Serum Ferritin and Vitamin-D Level in Coronary Artery Disease Patients. BIOMEDICAL AND PHARMACOLOGY JOURNAL 2023; 16:365-369. [DOI: 10.13005/bpj/2618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introduction: Coronary artery disease is one of the most common noncommunicable diseases that affects both men and women worldwide. Chronic inflammation and mineral nutrient deficiency, in addition to diet and sedentary lifestyle, contribute to this disease. The purpose of this study is to look at the relationship between serum ferritin, serum vitamin D levels, and serum lipid profile in patients with Coronary Artery Disease. Methods: The research was carried out at the Mahatma Gandhi Medical College and Research Institute in Puducherry. A standardised health questionnaire was distributed to study participants, which included 30 patients with Coronary Artery Disease (cases) and 30 healthy controls. It detailed current and previous medication use, hypertension, and coronary artery disease. Subjects were chosen based on their responses to study-related questions. For both cases and controls, means and standard deviations (SD) were computed. To determine the relationship between the parameters, ANOVA and Pearson's correlation were used, and it was used to find the statistical significance and correlation of Serum Ferritin, Serum Vitamin D, and Serum Lipid Profile among both groups. Results: The serum ferritin levels among cases (208.87±143.01 µg/lit) were found to be high when compared to controls (99.52 ± 61.19 µg/lit) with a significant p value of 0.0003. The Serum vitamin D value of cases (21.14 ± 12.9 ng/dl) was low when compared to controls (56.54 ± 18.88 ng/dl) with a significant p value of 0.0000. Serum LDL of cases (129.1 ± 26.91 mg/dl) were found to be higher than controls (105.1 ± 25.43 mg/dl). HDL of cases (33.83±6.82mg/dl) was found to be lower than controls (49.53±6.12 mg/dl). Conclusion: Altered lipid profile with low HDL-C, high LDL-C, and high LDL-C/HDL-C suggested an increased risk for CAD. Low vitamin D levels were also associated with a higher risk for CAD. According to this study, CAD patients had high serum ferritin levels, low serum vitamin D levels, and an altered lipid profile status.
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Affiliation(s)
- E. Vasudevan
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
| | - Mary Chandrika Anton
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
| | - B. Shanthi
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
| | - Chaganti Sridevi
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
| | - K. Sumathi
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
| | - Nivethini Nivethini
- Department of Biochemistry, Sree Balaji Medical College and Hospital, No.7 Works Road, Chrompet, Chennai, India
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20
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Zhang M, Zhang Z, Hu J, Zhou S, Ai W. Knockdown of long noncoding RNA MIAT attenuates hypoxia-induced cardiomyocyte injury by regulating the miR-488-3p/Wnt/β-catenin pathway. Cell Biol Int 2023; 47:63-74. [PMID: 36273414 DOI: 10.1002/cbin.11945] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 08/01/2022] [Accepted: 08/12/2022] [Indexed: 12/31/2022]
Abstract
Dysfunction of cardiomyocytes contributes to the development of acute myocardial infarction (AMI). Nonetheless, the regulatory mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in cardiomyocyte injury remains largely unclear. The cardiomyocyte injury was assessed via cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and flow cytometry, respectively. The levels of MIAT, microRNA (miR)-488-3p, and Wnt5a were detected via quantitative real-time polymerase chain reaction and Western blot. After bioinformatical analysis, the binding between miR-488-3p and MIAT or Wnt5a was confirmed via dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Our results showed that MIAT expression was increased in AC16 cells after hypoxia treatment. Silencing of MIAT alleviated hypoxia-induced viability reduction, apoptosis increase, and Wnt/β-catenin pathway activation. MIAT directly targeted miR-488-3p. MiR-488-3p might repress hypoxia-induced cardiomyocyte injury, and its knockdown reversed the effect of MIAT depletion on cardiomyocyte injury. Wnt5a was validated as a target of miR-488-3p. Wnt5a expression restoration attenuated the influence of MIAT knockdown on hypoxia-triggered cardiomyocyte injury. Our findings demonstrated that downregulation of MIAT might mitigate hypoxia-induced cardiomyocyte injury partly through miR-488-3p mediated Wnt/β-catenin pathway.
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Affiliation(s)
- Ming Zhang
- General Practice Medicine Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China
| | - Zhiling Zhang
- General Practice Medicine Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China
| | - Jie Hu
- General Practice Medicine Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China
| | - Shulan Zhou
- General Practice Medicine Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China
| | - Wenwei Ai
- General Practice Medicine Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China
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21
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Liu Y, Ye T, Chen K, Wu G, Xia Y, Wang X, Zong G. A nomogram risk prediction model for no-reflow after primary percutaneous coronary intervention based on rapidly accessible patient data among patients with ST-segment elevation myocardial infarction and its relationship with prognosis. Front Cardiovasc Med 2022; 9:966299. [PMID: 36003914 PMCID: PMC9393359 DOI: 10.3389/fcvm.2022.966299] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/19/2022] [Indexed: 11/26/2022] Open
Abstract
Background No-reflow occurring after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) can increase the incidence of major adverse cardiovascular events (MACE). The present study aimed to construct a nomogram prediction model that can be quickly referred to before surgery to predict the risk for no-reflow after PCI in STEMI patients, and to further explore its prognostic utility in this patient population. Methods Research subjects included 443 STEMI patients who underwent primary PCI between February 2018 and February 2021. Rapidly available clinical data obtained from emergency admissions were collected. Independent risk factors for no-reflow were analyzed using a multivariate logistic regression model. Subsequently, a nomogram for no-reflow was constructed and verified using bootstrap resampling. A receiver operating characteristic (ROC) curve was plotted to evaluate the discrimination ability of the nomogram model and a calibration curve was used to assess the concentricity between the model probability curve and ideal curve. Finally, the clinical utility of the model was evaluated using decision curve analysis. Results The incidence of no-reflow was 18% among patients with STEMI. Killip class ≥2 on admission, pre-operative D-dimer and fibrinogen levels, and systemic immune–inflammation index (SII) were independent risk factors for no-reflow. A simple and quickly accessible prediction nomogram for no-reflow after PCI was developed. This nomogram demonstrated good discrimination, with an area under the ROC curve of 0.716. This nomogram was further validated using bootstrapping with 1,000 repetitions; the C-index of the bootstrap model was 0.706. Decision curve analysis revealed that this model demonstrated good fit and calibration and positive net benefits. Kaplan–Meier survival curve analysis revealed that patients with higher model scores were at a higher risk of MACE. Multivariate Cox regression analysis revealed that higher model score(s) was an independent predictor of MACE (hazard ratio 2.062; P = 0.004). Conclusions A nomogram prediction model that can be quickly referred to before surgery to predict the risk for no-reflow after PCI in STEMI patients was constructed. This novel nomogram may be useful in identifying STEMI patients at higher risk for no-reflow and may predict prognosis in this patient population.
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Affiliation(s)
- Yehong Liu
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
| | - Ting Ye
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
| | - Ke Chen
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
- Wuxi Clinical College of Anhui Medical University, Wuxi, China
| | - Gangyong Wu
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
- Wuxi Clinical College of Anhui Medical University, Wuxi, China
| | - Yang Xia
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
| | - Xiao Wang
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
| | - Gangjun Zong
- Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, China
- Wuxi Clinical College of Anhui Medical University, Wuxi, China
- *Correspondence: Gangjun Zong
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22
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EVs predict the outcomes in patients with acute myocardial infarction. Tissue Cell 2022; 77:101857. [DOI: 10.1016/j.tice.2022.101857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 11/23/2022]
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23
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QIAN M, FENG ZQ, ZHENG RN, HU KW, SUN JZ, SUN HB, DAI L. Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis. Chin J Nat Med 2022; 20:432-442. [DOI: 10.1016/s1875-5364(22)60156-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Indexed: 11/27/2022]
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Gao H, Zhang L, Wang Z, Yan K, Zhao L, Xiao W. Research Progress on Transorgan Regulation of the Cardiovascular and Motor System through Cardiogenic Exosomes. Int J Mol Sci 2022; 23:ijms23105765. [PMID: 35628575 PMCID: PMC9146752 DOI: 10.3390/ijms23105765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 02/01/2023] Open
Abstract
The heart is the core organ of the circulatory system. Through the blood circulation system, it has close contact with all tissues and cells in the body. An exosome is an extracellular vesicle enclosed by a phospholipid bilayer. A variety of heart tissue cells can secrete and release exosomes, which transfer RNAs, lipids, proteins, and other biomolecules to adjacent or remote cells, mediate intercellular communication, and regulate the physiological and pathological activities of target cells. Cardiogenic exosomes play an important role in regulating almost all pathological and physiological processes of the heart. In addition, they can also reach distant tissues and organs through the peripheral circulation, exerting profound influence on their functional status. In this paper, the composition and function of cardiogenic exosomes, the factors affecting cardiogenic exosomes and their roles in cardiovascular physiology and pathophysiology are discussed, and the close relationship between cardiovascular system and motor system is innovatively explored from the perspective of exosomes. This study provides a reference for the development and application of exosomes in regenerative medicine and sports health, and also provides a new idea for revealing the close relationship between the heart and other organ systems.
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25
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Sia CH, Ko J, Zheng H, Ho AFW, Foo D, Foo LL, Lim PZY, Liew BW, Chai P, Yeo TC, Yip JWL, Chua T, Chan MYY, Tan JWC, Figtree G, Bulluck H, Hausenloy DJ. Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors. Front Cardiovasc Med 2022; 9:876465. [PMID: 35497977 PMCID: PMC9047915 DOI: 10.3389/fcvm.2022.876465] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/16/2022] [Indexed: 11/17/2022] Open
Abstract
Background Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed “SMuRF-less”) may be increasing in prevalence and have worse outcomes than “SMuRF-positive” patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes.
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Affiliation(s)
- Ching-Hui Sia
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Junsuk Ko
- MD Program, Duke-NUS Medical School, Singapore, Singapore
| | - Huili Zheng
- Health Promotion Board, National Registry of Diseases Office, Singapore, Singapore
| | - Andrew Fu-Wah Ho
- SingHealth Duke-NUS Emergency Medicine Academic Clinical Programme, Singapore, Singapore
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore
- Pre-hospital and Emergency Care Research Centre, Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore
| | - David Foo
- Tan Tock Seng Hospital, Singapore, Singapore
| | - Ling-Li Foo
- Health Promotion Board, National Registry of Diseases Office, Singapore, Singapore
| | | | | | - Ping Chai
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Tiong-Cheng Yeo
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - James W. L. Yip
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Terrance Chua
- Department of Cardiology, National Heart Centre Singapore, Singapore, Singapore
| | - Mark Yan-Yee Chan
- Department of Cardiology, National University Heart Centre Singapore, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jack Wei Chieh Tan
- Department of Cardiology, National Heart Centre Singapore, Singapore, Singapore
| | - Gemma Figtree
- Sydney Medical School (Northern), University of Sydney, Sydney, NSW, Australia
| | | | - Derek J. Hausenloy
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore
- The Hatter Cardiovascular Institute, University College London, London, United Kingdom
- Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taichung City, Taiwan
- *Correspondence: Derek J. Hausenloy
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El Agaty SM, Nassef NA, Abou-Bakr DA, Hanafy AA. Chronic activation of cardiac Atg-5 and pancreatic Atg-7 by intermittent fasting alleviates acute myocardial infarction in old rats. Egypt Heart J 2022; 74:31. [PMID: 35416562 PMCID: PMC9008107 DOI: 10.1186/s43044-022-00268-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 04/05/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Aging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO). RESULTS IF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats. CONCLUSIONS IF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.
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Affiliation(s)
- Sahar Mohamed El Agaty
- Department of Physiology, Medical Research Center, Faculty of Medicine, Ain Shams University, 24 Mohamed El Makaref Street, Nasr City, Cairo, Egypt.
| | - Noha A Nassef
- Department of Physiology, Medical Research Center, Faculty of Medicine, Ain Shams University, 24 Mohamed El Makaref Street, Nasr City, Cairo, Egypt
| | - Doaa A Abou-Bakr
- Department of Physiology, Medical Research Center, Faculty of Medicine, Ain Shams University, 24 Mohamed El Makaref Street, Nasr City, Cairo, Egypt
| | - Aya A Hanafy
- Department of Physiology, Medical Research Center, Faculty of Medicine, Ain Shams University, 24 Mohamed El Makaref Street, Nasr City, Cairo, Egypt
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27
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Deng HF, Zou J, Wang N, Ma H, Zhu LL, Liu K, Liu MD, Wang KK, Xiao XZ. Nicorandil alleviates cardiac remodeling and dysfunction post -infarction by up-regulating the nucleolin/autophagy axis. Cell Signal 2022; 92:110272. [PMID: 35122988 DOI: 10.1016/j.cellsig.2022.110272] [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: 11/03/2021] [Revised: 01/14/2022] [Accepted: 01/28/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The present study aimed to investigate whether the drug nicorandil can improve cardiac remodeling after myocardial infarction (MI) and the underlying mechanisms. METHODS Mouse MI was established by the ligation of the left anterior descending coronary artery and H9C2 cells were cultured to investigate the underlying molecular mechanisms. The degree of myocardial collagen (Col) deposition was evaluated by Masson's staining. The expressions of nucleolin, autophagy and myocardial remodeling-associated genes were measured by Western blotting, qPCR, and immunofluorescence. The apoptosis of myocardial tissue cells and H9C2 cells were detected by TUNEL staining and flow cytometry, respectively. Autophagosomes were observed by transmission electron microscopy. RESULTS Treatment with nicorandil mitigated left ventricular enlargement, improved the capacity of myocardial diastolic-contractility, decreased cardiomyocyte apoptosis, and inhibited myocardial fibrosis development post-MI. Nicorandil up-regulated the expression of nucleolin, promoted autophagic flux, and decreased the expressions of TGF-β1 and phosphorylated Smad2/3, while enhanced the expression of BMP-7 and phosphorylated Smad1 in myocardium. Nicorandil decreased apoptosis and promoted autophagic flux in H2O2-treated H9C2 cells. Autophagy inhibitors 3-methyladenine (3MA) and chloroquine diphosphate salt (CDS) alleviated the effects of nicorandil on apoptosis. Knockdown of nucleolin decreased the effects of nicorandil on apoptosis and nicorandil-promoted autophagic flux of cardiomyocytes treated with H2O2. CONCLUSIONS Treatment with nicorandil alleviated myocardial remodeling post-MI through up-regulating the expression of nucleolin, and subsequently promoting autophagy, followed by regulating TGF-β/Smad signaling pathway.
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Affiliation(s)
- Hua-Fei Deng
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China; Department of Pathophysiology, School of Basic Medical Science, Xiangnan University, Chenzhou, Hunan 423000, China
| | - Jiang Zou
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Nian Wang
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Heng Ma
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Li-Li Zhu
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Ke Liu
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Mei-Dong Liu
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China
| | - Kang-Kai Wang
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China.
| | - Xian-Zhong Xiao
- Department of Pathophysiology, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Key Laboratory of Sepsis Translational Medicine of Hunan, Central South University, Changsha, Hunan, China.
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Mao CY, Zhang TT, Li DJ, Zhou E, Fan YQ, He Q, Wang CQ, Zhang JF. Extracellular vesicles from hypoxia-preconditioned mesenchymal stem cells alleviates myocardial injury by targeting thioredoxin-interacting protein-mediated hypoxia-inducible factor-1α pathway. World J Stem Cells 2022; 14:183-199. [PMID: 35432732 PMCID: PMC8963381 DOI: 10.4252/wjsc.v14.i2.183] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/29/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Extracellular vesicles (EVs) derived from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) have better cardioprotective effects against myocardial infarction (MI) in the early stage than EVs isolated from normoxic (NC)-MSCs. However, the cardioprotective mechanisms of HP-EVs are not fully understood.
AIM To explore the cardioprotective mechanism of EVs derived from HP MSCs.
METHODS We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs (ADSCs) following hypoxia in vitro or MI in vivo, in order to improve the survival of cardiomyocytes (CMs) and restore cardiac function. The degree of CM apoptosis in each group was assessed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/PI assays. MicroRNA (miRNA) sequencing was used to investigate the functional RNA diversity between HP-EVs and NC-EVs from mouse ADSCs. The molecular mechanism of EVs in mediating thioredoxin-interacting protein (TXNIP) was verified by the dual-luciferase reporter assay. Co-immunoprecipitation, western blotting, and immunofluorescence were performed to determine if TXNIP is involved in hypoxia-inducible factor-1 alpha (HIF-1α) ubiquitination and degradation via the chromosomal region maintenance-1 (CRM-1)-dependent nuclear transport pathway.
RESULTS HP-EVs derived from MSCs reduced both infarct size (necrosis area) and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxia in vitro and mice with MI in vivo. Sequencing of EV-associated miRNAs showed the upregulation of 10 miRNAs predicted to bind TXNIP, an oxidative stress-associated protein. We showed miRNA224-5p, the most upregulated miRNA in HP-EVs, directly combined the 3’ untranslated region of TXNIP and demonstrated its critical protective role against hypoxia-mediated CM injury. Our results demonstrated that MI triggered TXNIP-mediated HIF-1α ubiquitination and degradation in the CRM-1-mediated nuclear transport pathway in CMs, which led to aggravated injury and hypoxia tolerance in CMs in the early stage of MI.
CONCLUSION The anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.
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Affiliation(s)
- Cheng-Yu Mao
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Tian-Tian Zhang
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Dong-Jiu Li
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - En Zhou
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Yu-Qi Fan
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Qing He
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Chang-Qian Wang
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
| | - Jun-Feng Zhang
- Department of Cardiology, Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200010, China
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Zhou W, Cai D. Midazolam suppresses ischemia/reperfusion-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway. Can J Physiol Pharmacol 2022; 100:117-124. [PMID: 34559975 DOI: 10.1139/cjpp-2021-0289] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Myocardial ischemia/reperfusion (I/R) injury causes irreversible injury to the heart, thereby causing acute myocardial infarction. Midazolam is a benzodiazepine commonly utilized in anesthesia and intensive care. Research has indicated that midazolam plays a critical role in many diseases; however, the function of midazolam in myocardial injury induced by I/R still needs further investigation. The infarct size and damage to the heart tissues were examined through 2,3,5-triphenyl tetrazolium chloride (TTC) staining and hematoxylin and eosin staining. The creatine kinase-myocardial band isoenzyme, lactate dehydrogenase, and aspartate aminotransferase levels were tested using commercial kits. Cell apoptosis was determined through TUNEL staining or flow cytometry assays. Bax, Bcl-2, cleaved caspase-3, phospho-38 (p-p38), p38, p-JNK, JNK, extracellular signal-regulated kinases (ERK), and p-ERK expression was examined through Western blot. In our study, midazolam was shown to suppress the infarct size and heart tissue damage and reduce myocardial enzyme leakage in I/R rats. Additionally, midazolam was found to retard cardiomyocyte apoptosis in I/R rats. The JNK/p38 MAPK signaling pathway in I/R rats was inhibited by midazolam. Our findings demonstrated that in hypoxia/reoxygenation (H/R) - mediated H9C2 cells, anisomycin abolished the suppressive effects of midazolam on the JNK/p38 MAPK signaling pathway. Next, exploration discovered that anisomycin abolished the cytoprotective effects of midazolam on H/R-treated H9C2 cell apoptosis. In conclusion, this work demonstrated that midazolam retarded I/R-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway. These results may provide new insight into the treatment of myocardial I/R injury.
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Affiliation(s)
- Weixiao Zhou
- Department of Anesthesiology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang 311800, China
- Department of Anesthesiology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang 311800, China
| | - Dongjiang Cai
- Department of Anesthesiology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang 311800, China
- Department of Anesthesiology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang 311800, China
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30
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Pinheiro-de-Sousa I, Fonseca-Alaniz MH, Teixeira SK, Rodrigues MV, Krieger JE. Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors. Sci Rep 2022; 12:1372. [PMID: 35079076 PMCID: PMC8789842 DOI: 10.1038/s41598-022-05404-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
Endothelial dysfunction (ED) is a hallmark of atherosclerosis and is influenced by well-defined risk factors, including hypoxia, dyslipidemia, inflammation, and oscillatory flow. However, the individual and combined contributions to the molecular underpinnings of ED remain elusive. We used global gene expression in human coronary artery endothelial cells to identify gene pathways and cellular processes in response to chemical hypoxia, oxidized lipids, IL-1β induced inflammation, oscillatory flow, and these combined stimuli. We found that clustering of the surrogate risk factors differed from the sum of the individual insults that gave rise to emergent phenotypes such as cell proliferation. We validated these observations in samples of human coronary artery atherosclerotic plaques analyzed using single-cell RNA sequencing. Our findings suggest a hierarchical interaction between surrogates of CV risk factors and the advent of emergent phenotypes in response to combined stimulation in endothelial cells that may influence ED.
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Affiliation(s)
- Iguaracy Pinheiro-de-Sousa
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Miriam H Fonseca-Alaniz
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Samantha K Teixeira
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Mariliza V Rodrigues
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Jose E Krieger
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
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lncRNA NRON knockdown alleviates hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis by upregulating HIF-1α expression. J Cardiovasc Pharmacol 2021; 79:479-488. [PMID: 34935702 DOI: 10.1097/fjc.0000000000001198] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 11/29/2021] [Indexed: 11/26/2022]
Abstract
ABSTRACT Acute myocardial infarction (AMI) has become the most common cause of death in the developed countries. However, its pathogenesis is poorly understood. Increasing studies have revealed that lncRNAs are important modulators of AMI development. This study aimed to explore the function of lncRNA noncoding repressor of nuclear factor of activated T cells (NRON) in hypoxia/reoxygenation (HR)-stimulated H9c2 cells. NRON expression in peripheral blood of AMI patients and H/R-stimulated H9c2 cells was measured by qRT-PCR. H9c2 cells were transfected with si-NRON or co-transfected with si-NRON and si-hypoxia-inducible factor-1 alpha (HIF-1α). The viability and apoptosis of these cells were evaluated by MTT assay and flow cytometer, respectively. In addition, HIF-1α, AKT/mTOR signal pathways, and ERK1/2 were detected by Western blot. NRON knockdown in the MI mouse model was conducted through adeno-associated virus (AAV) injection, and cardiac function was evaluated by motion-mode echocardiography. The results showed that NRON was highly expressed in peripheral blood of AMI patients and H/R-stimulated H9c2 cells. NRON knockdown promoted cell viability and inhibited cell apoptosis of H/R-stimulated H9c2 cells. Meanwhile, NRON knockdown also significantly attenuated heart damage and improved cardiac function in an AMI mouse model. Further, compared with si-normal control (NC), NRON knockdown increased the levels of HIF-1α, p-AKT, p-mTOR, and p-ERK1/2. HIF-1α knockdown reversed the effects of NRON knockdown in H/R-stimulated-H9c2 cells damage. Overall, our study revealed that NRON knockdown alleviated H/R-induced cardiomyocyte apoptosis by upregulating HIF-1α expression, suggesting that NRON might be a novel therapeutic target for AMI.
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Wen ZJ, Xin H, Wang YC, Liu HW, Gao YY, Zhang YF. Emerging roles of circRNAs in the pathological process of myocardial infarction. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 26:828-848. [PMID: 34729251 PMCID: PMC8536508 DOI: 10.1016/j.omtn.2021.10.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Myocardial infarction (MI) is defined as cardiomyocyte death in a clinical context consistent with ischemic insult. MI remains one of the leading causes of morbidity and mortality worldwide. Although there are a number of effective clinical methods for the diagnosis and treatment of MI, further investigation of novel biomarkers and molecular therapeutic targets is required. Circular RNAs (circRNAs), novel non-coding RNAs, have been reported to function mainly by acting as microRNA (miRNA) sponges or binding to RNA-binding proteins (RBPs). The circRNA-miRNA-mRNA (protein) regulatory pathway regulates gene expression and affects the pathological mechanisms of various diseases. Undoubtedly, a more comprehensive understanding of the relationship between MI and circRNA will lay the foundation for the development of circRNA-based diagnostic and therapeutic strategies for MI. Therefore, this review summarizes the pathophysiological process of MI and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.
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Affiliation(s)
- Zeng-Jin Wen
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hui Xin
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yong-Chen Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hao-Wen Liu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yan-Yan Gao
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yin-Feng Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
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Ye X, Hang Y, Lu Y, Li D, Shen F, Guan P, Dong J, Shi L, Hu W. CircRNA circ-NNT mediates myocardial ischemia/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression. Cell Death Dis 2021; 7:370. [PMID: 34845193 PMCID: PMC8630116 DOI: 10.1038/s41420-021-00706-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/06/2021] [Accepted: 10/04/2021] [Indexed: 11/09/2022]
Abstract
Pyroptosis has been implicated in the pathophysiology of myocardial infarction (MI) in rodents, but its contribution to reperfusion injury in MI patients is unclear. Here, we evaluated pyroptosis in MI patients in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. We also investigated the molecular mechanisms that regulate pyroptosis and myocardial I/R injury in these in vitro and in vivo models. The study showed that MI patients exhibited elevated serum concentrations of the pyroptosis-related pro-inflammatory cytokines IL-1β and IL-18. Increased levels of IL-1β and IL-18 as well as the pyroptosis-related inflammatory caspases (caspase-1 and 11) were detected in cultured cardiomyocytes after anoxia/reoxygenation (A/R) and in cardiac tissues after I/R. Circ-NNT and USP46 were upregulated while miR-33a-5p was downregulated in MI patients, as well as in cultured cardiomyocytes after A/R and cardiac tissues after I/R. Circ-NNT or USP46 knockdown or miR-33a-5p overexpression inhibited the expression of pro-caspase-1, cleaved caspase-1, pro-caspase-11, cleaved caspase-11, IL-1β, and IL-18 in A/R cardiomyocytes and attenuated myocardial infarction in I/R mice. The results from luciferase reporter assays and gene overexpression/knockdown studies indicated that miR-33a-5p directly targets USP46, and circ-NNT regulates USP46 by acting as a miR-33a-5p sponge. Direct association between circ-NNT and miR-33a-5p in cardiomyocytes was confirmed by pull-down assays. In summary, pyroptosis is activated during myocardial I/R and contributes to reperfusion injury. Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46. This circ-NNT→miR-33a-5p→USP46 signaling axis may serve as a potential target for the development of cardio-protective agents to improve the clinical outcome of reperfusion therapy.
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Affiliation(s)
- Xiaomiao Ye
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Yanwen Hang
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Yi Lu
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Dandan Li
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Fangfang Shen
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Ping Guan
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Jian Dong
- grid.8547.e0000 0001 0125 2443Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China
| | - Ludong Shi
- Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China.
| | - Wei Hu
- Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China.
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Alsahly MB, Zakari MO, Koch LG, Britton S, Katwa LC, Fisher-Wellman K, Lust RM. Augmented Cardiac Mitochondrial Capacity in High Capacity Aerobic Running "Disease-Resistant" Phenotype at Rest Is Lost Following Ischemia Reperfusion. Front Cardiovasc Med 2021; 8:752640. [PMID: 34805308 PMCID: PMC8595288 DOI: 10.3389/fcvm.2021.752640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/30/2021] [Indexed: 11/13/2022] Open
Abstract
Rationale: Regular active exercise is considered therapeutic for cardiovascular disease, in part by increasing mitochondrial respiratory capacity, but a significant amount of exercise capacity is determined genetically. Animal models, demonstrating either high capacity aerobic running (HCR) or low capacity aerobic running (LCR) phenotypes, have been developed to study the intrinsic contribution, with HCR rats subsequently characterized as "disease resistant" and the LCRs as "disease prone." Enhanced cardioprotection in HCRs has been variable and mutifactoral, but likely includes a metabolic component. These studies were conducted to determine the influence of intrinsic aerobic phenotype on cardiac mitochondrial function before and after ischemia and reperfusion. Methods: A total of 34 HCR and LCR rats were obtained from the parent colony at the University of Toledo, housed under sedentary conditions, and fed normal chow. LCR and HCR animals were randomly assigned to either control or ischemia-reperfusion (IR). On each study day, one HCR/LCR pair was anesthetized, and hearts were rapidly excised. In IR animals, the hearts were immediately flushed with iced hyperkalemic, hyperosmotic, cardioplegia solution, and subjected to global hypothermic ischemic arrest (80 min). Following the arrest, the hearts underwent warm reperfusion (120 min) using a Langendorff perfusion system. Following reperfusion, the heart was weighed and the left ventricle (LV) was isolated. A midventricular ring was obtained to estimate infarction size [triphenyltetrazolium chloride (TTC)] and part of the remaining tissue (~150 mg) was transferred to a homogenation buffer on ice. Isolated mitochondria (MITO) samples were prepared and used to determine respiratory capacity under different metabolic conditions. In control animals, MITO were obtained and prepared similarly immediately following anesthesia and heart removal, but without IR. Results: In the control rats, both resting and maximally stimulated respiratory rates were higher (32 and 40%, respectively; p < 0.05) in HCR mitochondria compared to LCR. After IR, resting MITO respiratory rates were decreased to about 10% of control in both strains, and the augmented capacity in HCRs was absent. Maximally stimulated rates also were decreased more than 50% from control and were no longer different between phenotypes. Ca++ retention capacity and infarct size were not significantly different between HCR and LCR (49.2 ± 5.6 vs. 53.7 ± 4.9%), nor was average coronary flow during reperfusion or arrhythmogenesis. There was a significant loss of mitochondria following IR, which was coupled with decreased function in the remaining mitochondria in both strains. Conclusion: Cardiac mitochondrial capacity from HCR was significantly higher than LCR in the controls under each condition. After IR insult, the cardiac mitochondrial respiratory rates were similar between phenotypes, as was Ca++ retention capacity, infarct size, and arrhythmogenicity, despite the increased mitochondrial capacity in the HCRs before ischemia. Relatively, the loss of respiratory capacity was actually greater in HCR than LCR. These data could suggest limits in the extent to which the HCR phenotype might be "protective" against acute tissue stressors. The extent to which any of these deficits could be "rescued" by adding an active exercise component to the intrinsic phenotype is unknown.
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Affiliation(s)
- Musaad B. Alsahly
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
- East Carolina Diabetes and Obesity Center, East Carolina University, Greenville, NC, United States
| | - Madaniah O. Zakari
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Lauren G. Koch
- Department of Physiology, College of Medicine, Taibah University, Medina, Saudi Arabia
| | - Steven Britton
- Department of Physiology and Pharmacology, University of Toledo, Toledo, OH, United States
| | - Laxmansa C. Katwa
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
| | - Kelsey Fisher-Wellman
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
- Departments of Anesthesiology and Molecular and Integrative Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Robert M. Lust
- Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
- Departments of Anesthesiology and Molecular and Integrative Medicine, University of Michigan, Ann Arbor, MI, United States
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Schumacher D, Liehn EA, Singh A, Curaj A, Wijnands E, Lira SA, Tacke F, Jankowski J, Biessen EA, van der Vorst EP. CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction. Biomedicines 2021; 9:1532. [PMID: 34829761 PMCID: PMC8614800 DOI: 10.3390/biomedicines9111532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 11/20/2022] Open
Abstract
Ischemia-reperfusion injury after the reopening of an occluded coronary artery is a major cause of cardiac damage and inflammation after acute myocardial infarction. The chemokine axis CCL20-CCR6 is a key player in various inflammatory processes, including atherosclerosis; however, its role in ischemia-reperfusion injury has remained elusive. Therefore, to gain more insight into the role of the CCR6 in acute myocardial infarction, we have studied cardiac injury after transient ligation of the left anterior descending coronary artery followed by reperfusion in Ccr6-/- mice and their respective C57Bl/6 wild-type controls. Surprisingly, Ccr6-/- mice demonstrated significantly reduced cardiac function and increased infarct sizes after ischemia/reperfusion. This coincided with a significant increase in cardiac inflammation, characterized by an accumulation of neutrophils and inflammatory macrophage accumulation. Chimeras with a bone marrow deficiency of CCR6 mirrored this adverse Ccr6-/- phenotype, while cardiac injury was unchanged in chimeras with stromal CCR6 deficiency. This study demonstrates that CCR6-dependent (bone marrow) cells exert a protective role in myocardial infarction and subsequent ischemia-reperfusion injury, supporting the notion that augmenting CCR6-dependent immune mechanisms represents an interesting therapeutic target.
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Affiliation(s)
- David Schumacher
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (D.S.); (A.C.); (J.J.); (E.A.L.B.)
- Department of Anesthesiology, University Hospital, RWTH Aachen University, 52074 Aachen, Germany
| | - Elisa A. Liehn
- Department of Intensive Care and Intermediate Care, University Hospital, RWTH Aachen University, 52074 Aachen, Germany;
- Department of Cardiology, Angiology and Intensive Medicine, University Hospital Aachen, 52074 Aachen, Germany
- National Institute for Pathology “Victor Babes”, 050096 Bucharest, Romania
- Institute for Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark
| | - Anjana Singh
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands; (A.S.); (E.W.)
- Cognizant Technology Solutions, Phase II Hinjawadi, Pune 411 057, Maharashtra, India
| | - Adelina Curaj
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (D.S.); (A.C.); (J.J.); (E.A.L.B.)
| | - Erwin Wijnands
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands; (A.S.); (E.W.)
| | - Sergio A. Lira
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Frank Tacke
- Department of Hepatology and Gastroenterolgy, Campus Virchow-Klinikum and Campus Charité Mitte, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Joachim Jankowski
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (D.S.); (A.C.); (J.J.); (E.A.L.B.)
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands; (A.S.); (E.W.)
| | - Erik A.L. Biessen
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (D.S.); (A.C.); (J.J.); (E.A.L.B.)
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands; (A.S.); (E.W.)
| | - Emiel P.C. van der Vorst
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (D.S.); (A.C.); (J.J.); (E.A.L.B.)
- Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands; (A.S.); (E.W.)
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336 Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336 Munich, Germany
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Overexpression of miR-1298 attenuates myocardial ischemia-reperfusion injury by targeting PP2A. J Thromb Thrombolysis 2021; 53:136-148. [PMID: 34351558 DOI: 10.1007/s11239-021-02540-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/20/2021] [Indexed: 10/20/2022]
Abstract
Previous studies reported that microRNA-1298 was abnormally expressed in the myocardium of rat hearts after hypoxia/normoxia injury. This study aims to investigate the function and specific mechanism of miR-1298 in myocardial ischemia/reperfusion (IR) injury. Neonatal rat cardiomyocytes (NRCMs) were isolated from neonatal rat hearts and subjected to oxygen/glucose deprivation/reperfusion (OGD/R) to induce I/R injury. The rat model with I/R injury was induced by ligating the proximal left anterior descending artery (LAD). MiR-1298 expression was detected by qRT-PCR. The levels of PP2A, Bcl-2, Bax, and AMPK signaling members (p-AMPK, p-GSK3β) was detected by Western blot. Cell apoptosis was evaluated by TUNEL staining assay and flow cytometry. The infarct size of rat hearts was assessed by TTC staining assay. Premature and mature MiR-1298 were significantly downregulated while PP2A was significantly upregulated during I/R injury both in vitro and in vivo. The prediction of Starbase suggested that PP2A was a potential target of miR-1298. MiR-1298 overexpression significantly reduced cardiomyocyte apoptosis in vitro, and its protective effect was obviously attenuated by PP2A overexpression. Luciferase reporter assay showed that miR-1298 targeted PP2A directly. In addition, miR-1298 overexpression significantly reduced infarct size and cardiomyocyte apoptosis in the hearts of rats received with I/R injury in vivo. Moreover, miR-1298 overexpression significantly elevated the levels of Bcl-2 and AMPK signaling members (p-AMPK, p-GSK3β) while decreased Bax level, and these effects were partially reversed by PP2A overexpression. MiR-1298 participated in myocardial I/R injury by targeting the PP2A/AMPK/GSK3β signaling pathway, suggesting that miR-1298 might be a potential therapeutic target for myocardial I/R injury.
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Alagarsamy KN, Mathan S, Yan W, Rafieerad A, Sekaran S, Manego H, Dhingra S. Carbon nanomaterials for cardiovascular theranostics: Promises and challenges. Bioact Mater 2021; 6:2261-2280. [PMID: 33553814 PMCID: PMC7829079 DOI: 10.1016/j.bioactmat.2020.12.030] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/15/2020] [Accepted: 12/31/2020] [Indexed: 12/13/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Heart attack and stroke cause irreversible tissue damage. The currently available treatment options are limited to "damage-control" rather than tissue repair. The recent advances in nanomaterials have offered novel approaches to restore tissue function after injury. In particular, carbon nanomaterials (CNMs) have shown significant promise to bridge the gap in clinical translation of biomaterial based therapies. This family of carbon allotropes (including graphenes, carbon nanotubes and fullerenes) have unique physiochemical properties, including exceptional mechanical strength, electrical conductivity, chemical behaviour, thermal stability and optical properties. These intrinsic properties make CNMs ideal materials for use in cardiovascular theranostics. This review is focused on recent efforts in the diagnosis and treatment of heart diseases using graphenes and carbon nanotubes. The first section introduces currently available derivatives of graphenes and carbon nanotubes and discusses some of the key characteristics of these materials. The second section covers their application in drug delivery, biosensors, tissue engineering and immunomodulation with a focus on cardiovascular applications. The final section discusses current shortcomings and limitations of CNMs in cardiovascular applications and reviews ongoing efforts to address these concerns and to bring CNMs from bench to bedside.
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Affiliation(s)
- Keshav Narayan Alagarsamy
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Sajitha Mathan
- Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), Department of Bioengineering, School of Chemical and Biotechnology, SASTRA University, Thanjavur, 613 401, Tamil Nadu, India
| | - Weiang Yan
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
- Section of Cardiac Surgery, Department of Surgery, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Alireza Rafieerad
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Saravanan Sekaran
- Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), Department of Bioengineering, School of Chemical and Biotechnology, SASTRA University, Thanjavur, 613 401, Tamil Nadu, India
| | - Hanna Manego
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Sanjiv Dhingra
- Regenerative Medicine Program, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
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Silva EAP, Santos DM, de Carvalho FO, Menezes IAC, Barreto AS, Souza DS, Quintans-Júnior LJ, Santos MRV. Monoterpenes and their derivatives as agents for cardiovascular disease management: A systematic review and meta-analysis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 88:153451. [PMID: 33483251 DOI: 10.1016/j.phymed.2020.153451] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/16/2020] [Accepted: 12/22/2020] [Indexed: 06/12/2023]
Abstract
BACKGROUND Monoterpenes are one of the most studied plant's secondary metabolites, they are found abundantly in essential oils of aromatic plants. They also have a great range of pharmacological properties, such as antihypertensive, bradycardic, antiarrhythmic and hypotensive. In the face of the burden caused by cardiovascular disease (CVDs) worldwide, studies using monoterpenes to assess their cardiovascular effects have increased over the years. PURPOSE This systematic review aimed to summarize the use of monoterpenes in animal models of any CVDs. METHODS PubMed, SCOPUS, LILACS and Web of Science databases were used to search for articles that used monoterpenes, in any type of administration, to treat or prevent CVDs in animal models. The PRISMA guidelines were followed. Two independent researchers extracted main characteristics of studies, methods and outcomes. Data obtained were analyzed qualitatively and quantitatively. RESULTS At the ending of the search process, 33 articles were selected for the systematic review. Of these, 17 articles were included in the meta-analysis. A total of 16 different monoterpenes were found for the treatment of hypertension, myocardial infarction, pulmonary hypertension, cardiac hypertrophy and arrhythmia. The main actions include hypotension, bradycardia, vasodilatation, antiarrhythmic, and antioxidant and antiapoptotic properties. From our data, it can be suggested that monoterpenes may be a significant source for new drug development. However, there is still a need to apply these knowledge into clinical research and a long path to pursue before putting them in the market. CONCLUSION The variability of cardiovascular effects demonstrated by the monoterpenes highlighted them as a promising candidates for treatment or prevention of CVDs. Nevertheless, studies that investigate their biological sites of action needs to be further encouraged.
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Affiliation(s)
- Eric Aian P Silva
- Department of Physiology, Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil; Biotechnology Graduate Program - Rede Nordeste de Biotecnologia (RENORBIO), Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil
| | - Danillo M Santos
- Department of Physiology, Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil; Health Sciences Graduate Program, Universidade Federal de Sergipe, Rua Claudio Batista S/N, Sanatorio, Aracaju-SE, 49.060-100, Brazil
| | - Fernanda Oliveira de Carvalho
- Department of Physiology, Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil; Health Sciences Graduate Program, Universidade Federal de Sergipe, Rua Claudio Batista S/N, Sanatorio, Aracaju-SE, 49.060-100, Brazil
| | - Igor A Cortes Menezes
- Hospital de Clínicas, Universidade Federal do Paraná, Rua General Carneiro, 181, Curitiba-PR, 80060-900, Brazil
| | - André S Barreto
- Department of Health Education, Universidade Federal de Sergipe, Av. Governador Marcelo Deda, 13, Centro, Lagarto-SE, CEP 49400-000, Brazil
| | - Diego S Souza
- Department of Anesthesiology, University of Arizona, Tucson, AZ, USA
| | - Lucindo J Quintans-Júnior
- Department of Physiology, Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil; Health Sciences Graduate Program, Universidade Federal de Sergipe, Rua Claudio Batista S/N, Sanatorio, Aracaju-SE, 49.060-100, Brazil
| | - Márcio R V Santos
- Department of Physiology, Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil; Health Sciences Graduate Program, Universidade Federal de Sergipe, Rua Claudio Batista S/N, Sanatorio, Aracaju-SE, 49.060-100, Brazil; Biotechnology Graduate Program - Rede Nordeste de Biotecnologia (RENORBIO), Universidade Federal de Sergipe, Av. Marechal Rondon, S/N, Cidade Universitaria, São Cristovao-SE, 49100-000, Brazil.
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Martin TP, MacDonald EA, Elbassioni AAM, O'Toole D, Zaeri AAI, Nicklin SA, Gray GA, Loughrey CM. Preclinical models of myocardial infarction: from mechanism to translation. Br J Pharmacol 2021; 179:770-791. [PMID: 34131903 DOI: 10.1111/bph.15595] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 11/28/2022] Open
Abstract
Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Preclinical animal models have significantly advanced our understanding of MI and have enabled the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in preclinical animal models. Despite this, preclinical models are limited in their ability to fully reproduce the complexity of MI in humans. The preclinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action and support translational medicine development.
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Affiliation(s)
- Tamara P Martin
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Eilidh A MacDonald
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Ali Ali Mohamed Elbassioni
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.,Suez Canal University, Arab Republic of Egypt
| | - Dylan O'Toole
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Ali Abdullah I Zaeri
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Stuart A Nicklin
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Gillian A Gray
- Centre for Cardiovascular Science, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK
| | - Christopher M Loughrey
- BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
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Xiao S, Zhou Y, Wu Q, Liu Q, Chen M, Zhang T, Zhu H, Liu J, Yin T, Pan D. FCER1G and PTGS2 Serve as Potential Diagnostic Biomarkers of Acute Myocardial Infarction Based on Integrated Bioinformatics Analyses. DNA Cell Biol 2021; 40:1064-1075. [PMID: 34115526 DOI: 10.1089/dna.2020.6447] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
This study aimed to explore the potential diagnostic biomarkers and mechanisms underlying acute myocardial infarction (AMI). We downloaded four datasets (GSE19339, GSE48060, GSE66360, and GSE97320) from the Gene Expression Omnibus database and combined them as an integrated dataset. A total of 153 differentially expressed genes (DEGs) were analyzed by the linear models for microarray analysis (LIMMA) package. Weighted gene co-expression network analysis was used to screen for the significant gene modules. The intersection of DEGs and genes in the most significant module was termed "common genes" (CGs). CGs were mainly enriched in "inflammatory response," "neutrophil chemotaxis," and "IL-17 signaling pathway" through functional enrichment analyses. Subsequently, 15 genes were identified as the hub genes in the protein-protein interaction network. The Fc fragment of IgE receptor Ig (FCER1G) and prostaglandin-endoperoxide synthase 2 (PTGS2) showed significantly increased expression in AMI patients and mice at the 12-h time point in our experiments. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of FCER1G and PTGS2. The area under ROC curve of FCER1G and PTGS2 was 77.6% and 80.7%, respectively. Moreover, the micro (mi)RNA-messenger (m)RNA network was also visualized; the results showed that miRNA-143, miRNA-144, and miRNA-26 could target PTGS2 in AMI progression.
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Affiliation(s)
- Shengjue Xiao
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yufei Zhou
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qi Wu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Qiaozhi Liu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Mengli Chen
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Tiantian Zhang
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Hong Zhu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jie Liu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Ting Yin
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Defeng Pan
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
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Ilov NN, Palnikova OV, Stompel DR, Nechepurenko АA. Clinical Predictors of Occurrence of Ventricular Tachyarrhythmias in Patients with Reduced Left Ventricle Ejection Fraction. Results of Single-Center Prospective Study. ACTA ACUST UNITED AC 2021; 61:32-40. [PMID: 34112073 DOI: 10.18087/cardio.2021.5.n1480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/21/2021] [Accepted: 02/26/2021] [Indexed: 11/18/2022]
Abstract
Aim To evaluate the diagnostic significance of clinical and demographic parameters for predicting a 2-year probability of ventricular tachyarrhythmias (VT) in patients with chronic heart failure and reduced left ventricular ejection fraction (CHFrLVEF).Material and methods This single-center, prospective cohort study included 175 patients with CHFrLVEF who were implanted with a cardioverter defibrillator (CD). The endpoint was a CD-detected episode of VT. Patients were followed up for 2 years with visits at 3, 12, and 24 months after CD implantation.Results The primary endpoint was observed in 43 (24.4 %) patients at an average of 20.9 months (95 % confidence interval (CI), 20-21.9). The 2-year risk of fatal ventricular arrhythmias increased with detection of unstable VT (one-factor analysis, odds ratio (OR), 4.2; 95 % CI, 1.1-16.5; р=0.041; multifactor analysis, OR, 6.3; 95 % CI, 1.5-26.3; р=0.012) and with ischemic CHFrLVEF origin (one-factor analysis, OR, 2.2; 95 % CI, 1.1-4.5; p=0.021; multifactor analysis, OR, 2.5; 95 % CI, 1.2-5.1; р=0.018). In the presence of any type of atrial fibrillation (AF) in patients with non-ischemic CHFrLVEF, the probability of VT increased threefold (one-factor analysis, OR, 2.97; 95 % CI, 1.02-8.8; р=0.047; multifactor analysis, OR, 3.5; 95 % CI, 1.1-10.9; р=0.032).Conclusion The presence of ischemic heart disease and unstable VT paroxysms can be included in the number of important clinical predictors of VT in patients with CHFrLVEF. In patients with non-ischemic CHF, the presence of AF is associated with a high risk of VT.
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Affiliation(s)
- N N Ilov
- Astrakhan State Medical University, Astrakhan; Federal Center for Cardiovascular Surgery, Astrakhan
| | - O V Palnikova
- Federal Center for Cardiovascular Surgery, Astrakhan
| | - D R Stompel
- Federal Center for Cardiovascular Surgery, Astrakhan
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Ellman DG, Slaiman IM, Mathiesen SB, Andersen KS, Hofmeister W, Ober EA, Andersen DC. Apex Resection in Zebrafish ( Danio rerio) as a Model of Heart Regeneration: A Video-Assisted Guide. Int J Mol Sci 2021; 22:5865. [PMID: 34070781 PMCID: PMC8199168 DOI: 10.3390/ijms22115865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 11/17/2022] Open
Abstract
Ischemic heart disease is one of the leading causes of deaths worldwide. A major hindrance to resolving this challenge lies in the mammalian hearts inability to regenerate after injury. In contrast, zebrafish retain a regenerative capacity of the heart throughout their lifetimes. Apex resection (AR) is a popular zebrafish model for studying heart regeneration, and entails resecting 10-20% of the heart in the apex region, whereafter the regeneration process is monitored until the heart is fully regenerated within 60 days. Despite this popularity, video tutorials describing this technique in detail are lacking. In this paper we visualize and describe the entire AR procedure including anaesthesia, surgery, and recovery. In addition, we show that the concentration and duration of anaesthesia are important parameters to consider, to balance sufficient levels of sedation and minimizing mortality. Moreover, we provide examples of how zebrafish heart regeneration can be assessed both in 2D (immunohistochemistry of heart sections) and 3D (analyses of whole, tissue cleared hearts using multiphoton imaging). In summary, this paper aims to aid beginners in establishing and conducting the AR model in their laboratory, but also to spur further interest in improving the model and its evaluation.
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Affiliation(s)
- Ditte Gry Ellman
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
| | - Ibrahim Mohamad Slaiman
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
| | - Sabrina Bech Mathiesen
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
| | - Kristian Skriver Andersen
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
| | - Wolfgang Hofmeister
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
- Faculty of Health and Medical Sciences, DanStem (Novo Nordisk Foundation Center for Stem Cell Biology), Blegdamsvej 3B, 2200 København H, Denmark;
| | - Elke Annette Ober
- Faculty of Health and Medical Sciences, DanStem (Novo Nordisk Foundation Center for Stem Cell Biology), Blegdamsvej 3B, 2200 København H, Denmark;
| | - Ditte Caroline Andersen
- DCA-Lab, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, J. B. Winsløwsvej 25, 1. Floor, 5000 Odense C, Denmark; (D.G.E.); (I.M.S.); (S.B.M.); (K.S.A.); (W.H.)
- DCA-Lab, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 19, 5000 Odense C, Denmark
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The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B. Biosci Rep 2021; 40:221736. [PMID: 31894853 PMCID: PMC6970065 DOI: 10.1042/bsr20191000] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 12/03/2019] [Accepted: 12/17/2019] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.
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Usefulness of Estimated Pulse Wave Velocity in Prediction of Cardiovascular Mortality in Patients With Acute Myocardial Infarction. Am J Med Sci 2021; 361:479-484. [PMID: 33637306 DOI: 10.1016/j.amjms.2020.10.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 07/07/2020] [Accepted: 10/22/2020] [Indexed: 11/23/2022]
Abstract
BACKGROUND Pulse wave velocity (PWV) is an excellent index of arterial stiffness and can be used to predict long-term cardiovascular (CV) outcome. In recent years, estimated PWV (ePWV), calculated by equations using age and mean blood pressure, was also reported to be a significant predictor of CV outcomes. However, there was no literature discussing about usefulness of ePWV in patients of acute myocardial infarction (AMI) for prediction of long-term CV and overall mortality. Therefore, we conducted this study for further evaluation. METHODS A total of 187 patients with AMI admitted to cardiac care unit were enrolled. ePWV were calculated by the equations for each patient. RESULTS The median follow-up to mortality was 73 months (25th-75th percentile: 8-174 months). There were 35 and 125 patients documented as CV and overall mortality, respectively. Under univariable analysis, ePWV could independently predict long-term CV and overall mortality. However, after multivariable analysis, ePWV could only predict long-term CV mortality in AMI patients. CONCLUSIONS To the best of our knowledge, our study was the first to evaluate the usefulness of ePWV in AMI patients for prediction of long-term CV and overall mortality. Our study showed ePWV was not only easy to calculate by formula, but also an independent predictor for long-term CV mortality in univariable and multivariable analyses. Therefore, ePWV was a simple and useful tool to measure arterial stiffness and to predict CV mortality outcome in AMI patients without the necessity for equipment to measure PWV.
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Portillo Esquivel LE, Zhang B. Application of Cell, Tissue, and Biomaterial Delivery in Cardiac Regenerative Therapy. ACS Biomater Sci Eng 2021; 7:1000-1021. [PMID: 33591735 DOI: 10.1021/acsbiomaterials.0c01805] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cardiovascular diseases (CVD) are the leading cause of death around the world, being responsible for 31.8% of all deaths in 2017 (Roth, G. A. et al. The Lancet 2018, 392, 1736-1788). The leading cause of CVD is ischemic heart disease (IHD), which caused 8.1 million deaths in 2013 (Benjamin, E. J. et al. Circulation 2017, 135, e146-e603). IHD occurs when coronary arteries in the heart are narrowed or blocked, preventing the flow of oxygen and blood into the cardiac muscle, which could provoke acute myocardial infarction (AMI) and ultimately lead to heart failure and death. Cardiac regenerative therapy aims to repair and refunctionalize damaged heart tissue through the application of (1) intramyocardial cell delivery, (2) epicardial cardiac patch, and (3) acellular biomaterials. In this review, we aim to examine these current approaches and challenges in the cardiac regenerative therapy field.
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Affiliation(s)
| | - Boyang Zhang
- Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.,School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontaria L8S 4L8, Canada
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Huang L, Xu DQ, Chen YY, Yue SJ, Tang YP. Leonurine, a potential drug for the treatment of cardiovascular system and central nervous system diseases. Brain Behav 2021; 11:e01995. [PMID: 33300684 PMCID: PMC7882174 DOI: 10.1002/brb3.1995] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 11/17/2020] [Accepted: 11/20/2020] [Indexed: 12/13/2022] Open
Abstract
Leonurus japonicus Houtt., a traditional Chinese herbal medicine, is often used as a gynecological medicine with the effect of promoting blood circulation, regulating menstruation, clearing heat, and detoxificating. As the most important alkaloid in L. japonicus, leonurine has a wide range of biological activities, such as antioxidation, anti-inflammation, and anti-apoptosis. Cardiovascular system and central nervous system diseases are arrogant killers that threaten human lives and health around the world, but many drugs for treating them have certain side effects. This paper reviews the potential therapeutic effects of leonurine on cardiovascular system and central nervous system diseases, summarizes the previous research progress, and focuses on its therapeutic effect in various diseases. Although leonurine plays a prominent role in the treatment of cardiovascular system and central nervous system diseases, there are still some shortages, such as low bioavailability, weak transmembrane ability, and poor fat solubility. Therefore, the structure modification of leonurine may solve these problems and provide reference value for the development of new drugs. At present, leonurine is in clinical trial, and it is hoped that our summary will help to provide guidance for its future research on the basic science and clinical application.
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Affiliation(s)
- Lu Huang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Yan-Yan Chen
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Shi-Jun Yue
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China
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Isgut M, Sun J, Quyyumi AA, Gibson G. Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later. Genome Med 2021; 13:13. [PMID: 33509272 PMCID: PMC7845089 DOI: 10.1186/s13073-021-00828-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/07/2021] [Indexed: 01/09/2023] Open
Abstract
Background Several polygenic risk scores (PRS) have been developed for cardiovascular risk prediction, but the additive value of including PRS together with conventional risk factors for risk prediction is questionable. This study assesses the clinical utility of including four PRS generated from 194, 46K, 1.5M, and 6M SNPs, along with conventional risk factors, to predict risk of ischemic heart disease (IHD), myocardial infarction (MI), and first MI event on or before age 50 (early MI). Methods A cross-validated logistic regression (LR) algorithm was trained either on ~ 440K European ancestry individuals from the UK Biobank (UKB), or the full UKB population, including as features different combinations of conventional established-at-birth risk factors (ancestry, sex) and risk factors that are non-fixed over an individual’s lifespan (age, BMI, hypertension, hyperlipidemia, diabetes, smoking, family history), with and without also including PRS. The algorithm was trained separately with IHD, MI, and early MI as prediction labels. Results When LR was trained using risk factors established-at-birth, adding the four PRS significantly improved the area under the curve (AUC) for IHD (0.62 to 0.67) and MI (0.67 to 0.73), as well as for early MI (0.70 to 0.79). When LR was trained using all risk factors, adding the four PRS only resulted in a significantly higher disease prevalence in the 98th and 99th percentiles of both the IHD and MI scores. Conclusions PRS improve cardiovascular risk stratification early in life when knowledge of later-life risk factors is unavailable. However, by middle age, when many risk factors are known, the improvement attributed to PRS is marginal for the general population. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-021-00828-8.
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Affiliation(s)
- Monica Isgut
- School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, EBB1 Suite 2115, Georgia Tech, Atlanta, GA, 30332, USA
| | - Jimeng Sun
- Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, USA
| | - Arshed A Quyyumi
- Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, USA
| | - Greg Gibson
- School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, EBB1 Suite 2115, Georgia Tech, Atlanta, GA, 30332, USA.
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Carvalho de Campos Martins E, Luiz de Melo Bernardi F, Maia Junior OT, Micari A, Hopkins LN, Cremonesi A, Castriota F. Similarities and Differences Between Primary Percutaneous Coronary Intervention and Mechanical Thrombectomy. JACC Cardiovasc Interv 2021; 13:1683-1696. [PMID: 32703592 DOI: 10.1016/j.jcin.2020.03.055] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/27/2020] [Accepted: 03/31/2020] [Indexed: 02/06/2023]
Abstract
Acute ischemic stroke is among the leading causes of mortality and disability worldwide. Since 2015, as was the case for primary percutaneous coronary intervention for acute myocardial infarction, catheter-based reperfusion via mechanical thrombectomy (MT) has become the gold-standard treatment for acute ischemic stroke caused by large-vessel occlusion. Despite that, only a fraction of the world's population currently would be able to undergo MT in time, mostly because of the scarcity of 24/7 coverage by neurointerventionalists to deal with this enormous burden. Interventional cardiologists have thus been considered a logical option to aid in combating this vast demand to diminish the burden of acute ischemic stroke. However, despite some seemingly evident similarities between primary percutaneous coronary intervention and MT, for interventional cardiologists to enter this new field, they must be well trained and fully aware of all the clinical, technical, and environmental differences between these two scenarios. The main objective of this state-of-the-art paper is to serve as an introductory and comprehensive guide to familiarize the interventional cardiology community with the most critical technical aspects of MT.
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Affiliation(s)
| | | | | | - Antonio Micari
- Cardiovascular Unit, Humanitas Gavazzeni Hospital, Bergamo, Italy
| | - Leo Nelson Hopkins
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York; Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York; Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, New York; Jacobs Institute, Buffalo, New York
| | | | - Fausto Castriota
- Cardiovascular Unit, Humanitas Gavazzeni Hospital, Bergamo, Italy
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Yang H, Liu S, Du H, Hong Z, Lv Y, Nie C, Yang W, Gao Y. Hydrogen Attenuates Myocardial Injury in Rats by Regulating Oxidative Stress and NLRP3 Inflammasome Mediated Pyroptosis. Int J Med Sci 2021; 18:3318-3325. [PMID: 34400901 PMCID: PMC8364469 DOI: 10.7150/ijms.61329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 07/16/2021] [Indexed: 11/26/2022] Open
Abstract
Purpose: Hydrogen (H2) is an antioxidant with anti-inflammatory and apoptosis functions.This study aimed to estimate the effects of H2 on acute myocardial infarction (AMI) in rats and its association with the inhibition of oxidative stress and cardiomyocyte pyroptosis. Methods: Sixty-four rats were randomly divided into three groups (Sham, AMI, and H2). The left anterior descending coronary artery (LAD) of rats in the AMI and H2 groups was ligated, while rats in the Sham group were threaded without ligation. In addition, 2% H2 was administered by inhalation for 24 h after ligation in the H2 group. Transthoracic echocardiography was performed after H2 inhalation, followed by collection of the serum and cardiac tissue of all rats. Results: H2 inhalation ameliorated the cardiac dysfunction, infarct size and inflammatory cell infiltration caused by AMI. Meanwhile, H2 inhalation reduced the concentration of serum Troponin I (TnI), brain natriuretic peptide (BNP), reactive oxygen species (ROS), cardiac malondialdehyde (MDA), and 8-OHdG. In addition, H2 inhalation inhibited cardiac inflammation and pyroptosis relative proteins expression. Conclusion: H2 effectively promoted heart functions in AMI rats by regulating oxidative stress and pyroptosis.
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Affiliation(s)
- Hongxiao Yang
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Shuang Liu
- Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Huijun Du
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Zi Hong
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yajing Lv
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Chaoqun Nie
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Wei Yang
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yunan Gao
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Ambra1 Alleviates Hypoxia/Reoxygenation Injury in H9C2 Cells by Regulating Autophagy and Reactive Oxygen Species. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3062689. [PMID: 33083461 PMCID: PMC7563064 DOI: 10.1155/2020/3062689] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 09/08/2020] [Accepted: 09/21/2020] [Indexed: 11/24/2022]
Abstract
Reperfusion therapy is the most important method for treating acute myocardial infarction. However, myocardial ischemia reperfusion injury (MIRI) can offset the benefit of reperfusion therapy and worsen the outcome. In both ischemia and reperfusion, autophagy remains problematic. Activating molecule in Beclin1-regulated autophagy (Ambra1) is an important protein in autophagy regulation, and its function in MIRI remains unclear. Thus, we used H9C2 cells to investigate the function of Ambra1 in MIRI and the underlying mechanisms involved. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro. During hypoxia, autophagy flux was blocked, then recovered in reoxygenation. Ambra1 overexpression increased autophagy in the H9C2 cells, as the LC3B II/I ratio increased, and alleviated cellular necrosis and apoptosis during hypoxia and reoxygenation. This effect was counteracted by an autophagy inhibitor. Knocking down Ambra1 can block autophagy which P62 sediment/supernatant ratio increased while the ratio of LC3B II/I decreased, and worsen outcomes. Ambra1 enhances autophagy in H9C2 cells by improving the stability and activity of the ULK1 complex. Reactive oxygen species (ROS) are an important cause of MIRI. ROS were reduced when Ambra1 was overexpressed and increased when Ambra1 was knocked down, indicating that Ambra1 can protect against hypoxia and reoxygenation injury in H9C2 cells by promoting autophagy and reducing ROS.
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