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Yan D, Zhan S, Guo C, Han J, Zhan L, Zhou Q, Bing D, Wang X. The role of myocardial regeneration, cardiomyocyte apoptosis in acute myocardial infarction: A review of current research trends and challenges. J Cardiol 2025; 85:283-292. [PMID: 39393490 DOI: 10.1016/j.jjcc.2024.09.012] [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: 05/21/2024] [Revised: 09/30/2024] [Accepted: 09/30/2024] [Indexed: 10/13/2024]
Abstract
PURPOSE This paper aims to review the research progress in repairing injury caused by acute myocardial infarction, focusing on myocardial regeneration, cardiomyocyte apoptosis, and fibrosis. The goal is to investigate the current research trends and challenges in the field of myocardial injury repair. METHODS The review delves into the latest research on myocardial regeneration, cardiomyocyte apoptosis, and fibrosis following acute myocardial infarction. It highlights stem cell transplantation and gene therapy as key areas of current research focus, while emphasizing the significance of cardiomyocyte apoptosis and fibrosis in the myocardial injury repair process. Additionally, the review addresses the challenges and unresolved issues that require further investigation in the field of myocardial injury repair. SUMMARY Acute myocardial infarction is a prevalent cardiovascular condition that results in myocardial damage necessitating repair. Myocardial regeneration plays a crucial role in repairing myocardial injury, with current research focusing on stem cell transplantation and gene therapy. Cardiomyocyte apoptosis and fibrosis are key factors in the repair process, significantly impacting the restoration of myocardial structure and function. Nonetheless, there remain numerous challenges and unresolved issues that warrant further investigation in the realm of myocardial injury repair.
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Affiliation(s)
- Dan Yan
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China; Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China; Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China.
| | - Shifang Zhan
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Chenyu Guo
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Jiawen Han
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Lin Zhan
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Qianyi Zhou
- Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China
| | - Dan Bing
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xiaoyan Wang
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, China.
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Xie Z, Luo H, Wang T, Wang L, Zhang J, Dong W, Liu G, Li F, Kang Q, Zhu X, Zhang F, Peng W. METTL3 inhibits BMSC apoptosis and facilitates osteonecrosis repair via an m6A-IGF2BP2-dependent mechanism. Heliyon 2024; 10:e30195. [PMID: 38784565 PMCID: PMC11112270 DOI: 10.1016/j.heliyon.2024.e30195] [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: 02/23/2024] [Revised: 04/19/2024] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Hypoxia-induced apoptosis of bone marrow mesenchymal stem cells (BMSCs) limits the efficacy of their transplantation for steroid-induced osteonecrosis of the femoral head (SONFH). As apoptosis and RNA methylation are closely related, exploring the role and mechanism of RNA methylation in hypoxic apoptosis of BMSCs is expected to identify new targets for transplantation of BMSCs for SONFH and enhance transplantation efficacy. We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA-seq on a hypoxia-induced apoptosis BMSC model and found that the RNA methyltransferase-like 3 (METTL3) is involved in hypoxia-induced BMSC apoptosis. The expression of METTL3 was downregulated in BMSCs after hypoxia and in BMSCs implanted in osteonecrosis areas. Knockdown of METLL3 under normoxic conditions promoted apoptosis of BMSCs. In contrast, overexpression of METTL3 promoted the survival of BMSCs under hypoxic conditions, and overexpression of METTL3 promoted the survival of BMSCs in the osteonecrosis area and the repair of the osteonecrosis area. Regarding the mechanism, the m6A levels of the mRNAs of anti-apoptotic genes Bcl-2, Mcl-1, and BIRC5 were significantly increased upon the overexpression of METTL3 under hypoxic conditions, which promoted the binding of Bcl-2, Mcl-1, and BIRC5 mRNAs to IGF2BP2, enhanced the mRNA stability, and increased the protein expression of the three anti-apoptotic genes. In conclusion, overexpression of METTL3 promoted m6A modification of mRNAs of Bcl-2, Mcl-1, and BIRC5, promoted the binding of IGF2BP2 to the above-mentioned mRNAs, enhanced mRNA stability, inhibited hypoxia-induced BMSC apoptosis, and promoted repair of SONFH, thereby providing novel targets for transplantation of BMSCs for SONFH.
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Affiliation(s)
- Zhihong Xie
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Hong Luo
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Tao Wang
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Lei Wang
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Jian Zhang
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Wentao Dong
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Gang Liu
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Fanchao Li
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Qinglin Kang
- Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Xuesong Zhu
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Fei Zhang
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
| | - Wuxun Peng
- Department of Emergency Orthopedics, The Affliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China
- School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China
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Berezin AE, Berezin AA. Extracellular vesicles in heart failure. Adv Clin Chem 2024; 119:1-32. [PMID: 38514208 DOI: 10.1016/bs.acc.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
Physiologically, extracellular vesicles (EVs) have been implicated as crucial mediators of immune response, cell homeostasis, angiogenesis, cell differentiation and growth, and tissue repair. In heart failure (HF) they may act as regulators of cardiac remodeling, microvascular inflammation, micro environmental changes, tissue fibrosis, atherosclerosis, neovascularization of plaques, endothelial dysfunction, thrombosis, and reciprocal heart-remote organ interaction. The chapter summaries the nomenclature, isolation, detection of EVs, their biologic role and function physiologically as well as in the pathogenesis of HF. Current challenges to the utilization of EVs as diagnostic and predictive biomarkers in HF are also discussed.
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Affiliation(s)
- Alexander E Berezin
- Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
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You B, Yang Y, Zhou Z, Yan Y, Zhang L, Jin J, Qian H. Extracellular Vesicles: A New Frontier for Cardiac Repair. Pharmaceutics 2022; 14:pharmaceutics14091848. [PMID: 36145595 PMCID: PMC9503573 DOI: 10.3390/pharmaceutics14091848] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 11/16/2022] Open
Abstract
The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been used to treat diseases. Growing evidence indicates that EVs play a cardioprotective role in heart disease by activating beneficial signaling pathways. Multiple functional components of EVs and intracellular molecular mechanisms are involved in the process. To overcome the shortcomings of native EVs such as their heterogeneity and limited tropism, a series of engineering approaches has been developed to improve the therapeutic efficiency of EVs. In this review, we present an overview of the research and future directions for EVs-based cardiac therapies with an emphasis on EVs-mediated delivery of therapeutic agents. The advantages and limitations of various modification strategies are discussed, and possible opportunities for improvement are proposed. An in-depth understanding of the endogenous properties of EVs and EVs engineering strategies could lead to a promising cell-free therapy for cardiac repair.
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Affiliation(s)
- Benshuai You
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Yang Yang
- Clinical Laboratory Center, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou 225317, China
| | - Zixuan Zhou
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Yongmin Yan
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China
| | - Leilei Zhang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Jianhua Jin
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China
- Correspondence: (J.J.); (H.Q.)
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
- Correspondence: (J.J.); (H.Q.)
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Repetitive Treatment with Volatile Anesthetics Does Not Affect the In Vivo Plasma Concentration and Composition of Extracellular Vesicles in Rats. Curr Issues Mol Biol 2021; 43:1997-2010. [PMID: 34889902 PMCID: PMC8929111 DOI: 10.3390/cimb43030137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/04/2021] [Accepted: 11/10/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Anesthetic-induced preconditioning (AIP) with volatile anesthetics is a well-known experimental technique to protect tissues from ischemic injury or oxidative stress. Additionally, plasmatic extracellular vesicle (EV) populations and their cargo are known to be affected by AIP in vitro, and to provide organ protective properties via their cargo. We investigated whether AIP would affect the generation of EVs in an in vivo rat model. Methods: Twenty male Sprague Dawley rats received a repetitive treatment with either isoflurane or with sevoflurane for a duration of 4 or 8 weeks. EVs from blood plasma were characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM) and Western blot. A scratch assay (H9C2 cardiomyoblast cell line) was performed to investigate the protective capabilities of the isolated EVs. Results: TEM images as well as Western blot analysis indicated that EVs were successfully isolated. The AIP changed the flotillin and CD63 expression on the EV surface, but not the EV concentration. The scratch assay did not show increased cell migration and/or proliferation after EV treatment. Conclusion: AIP in rats changed the cargo of EVs but had no effect on EV concentration or cell migration/proliferation. Future studies are needed to investigate the cargo on a miRNA level and to investigate the properties of these EVs in additional functional experiments.
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miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells. J Immunol Res 2021; 2021:6744715. [PMID: 34746322 PMCID: PMC8570887 DOI: 10.1155/2021/6744715] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 09/24/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022] Open
Abstract
Background Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.
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