Murine exosomal miR-30a aggravates cardiac function after acute myocardial infarction via regulating cell fate of cardiomyocytes and cardiac resident macrophages.

Autor: Li YY; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: yyli0224@126.com., Chen HR; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China., Yang Y; Department of General, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China., Pan YJ; Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China., Yuan QC; Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida, USA., Liu YZ; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: yzhliu09@163.com.
Jazyk: angličtina
Zdroj: International journal of cardiology [Int J Cardiol] 2024 Nov 01; Vol. 414, pp. 132395. Date of Electronic Publication: 2024 Jul 27.
DOI: 10.1016/j.ijcard.2024.132395
Abstrakt: After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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