1. Dysregulation of miR-342-3p in plasma exosomes derived from convalescent AMI patients and its consequences on cardiac repair
- Author
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Chang Cao, Yunzhe Wang, Zeng-Lei Zhang, Jian-Chao Zhang, Qian-Qian Guo, Deliang Shen, Jing Bai, Jin-Ying Zhang, Bo Wang, Jiacheng Guo, Dongjian Han, Junnan Tang, and Demin Li
- Subjects
Adult ,Male ,Cardiotonic Agents ,Cell Survival ,media_common.quotation_subject ,Myocardial Infarction ,Down-Regulation ,Apoptosis ,Acute myocardial infarction ,RM1-950 ,Exosomes ,Cell Line ,Rats, Sprague-Dawley ,Cardiac repair ,In vivo ,Autophagy ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,cardiovascular diseases ,Myocardial infarction ,media_common ,Pharmacology ,Biological Products ,MiR-342-3p ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,business.industry ,Convalescence ,Hydrogen Peroxide ,General Medicine ,Middle Aged ,medicine.disease ,Microvesicles ,In vitro ,Disease Models, Animal ,MicroRNAs ,Cancer research ,TFEB ,Female ,Therapeutics. Pharmacology ,business ,SOXD Transcription Factors - Abstract
Plasma exosomes derived from healthy people have been shown to be beneficial in terms of protecting against ischemia-reperfusion injury or acute myocardial infarction (AMI). However, a pathological condition may severely affect the constitution and biological activity of exosomes. In our study, we isolated plasma exosomes from healthy volunteers and convalescent AMI patients (3–7 d after onset). Compared to exosomes from healthy controls (Nor-Exo), exosomes from convalescent AMI patients (AMI-Exo) exhibited an impaired ability to repair damaged cardiomyocytes both in vitro and in vivo. miRNA sequencing and PCR analysis indicated that miR-342-3p was significantly downregulated in AMI-Exo. Moreover, miR-342-3p alleviated H2O2-induced injury and reduced apoptosis and autophagy in H9c2 cardiomyocytes, while in vivo restoration of miR-342-3p expression enhanced the reparative function of AMI-Exo. Further mechanistic studies revealed that the SOX6 and TFEB genes were two direct and functional targets of miR-342-3p. Taken together, during the early convalescent phase after AMI, dysregulated miR-342-3p in plasma exosomes might be responsible for their impaired cardioprotective potential. miR-342-3p contributed to exosome-mediated heart repair by inhibiting cardiomyocyte apoptosis and autophagy through targeting SOX6 and TFEB, respectively. Our work provided novel insights on the role of plasma exosomes in the natural process of cardiac repair after AMI and suggestions for therapy development.
- Published
- 2021