Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, PR China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, PR China.
Biomed Pharmacother. 2021 Oct;142:112056. doi: 10.1016/j.biopha.2021.112056. Epub 2021 Aug 23.
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 HO-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.
从健康人血浆中提取的外泌体在预防缺血再灌注损伤或急性心肌梗死（AMI）方面表现出有益作用。然而，病理状况可能会严重影响外泌体的组成和生物活性。在我们的研究中，我们从健康志愿者和 AMI 恢复期患者（发病后 3-7 天）中分离了血浆外泌体。与健康对照组（Nor-Exo）的外泌体相比，AMI 恢复期患者（AMI-Exo）的外泌体在体外和体内修复受损心肌细胞的能力受损。miRNA 测序和 PCR 分析表明，AMI-Exo 中 miR-342-3p 显著下调。此外，miR-342-3p 减轻了 HO 诱导的损伤，并减少了 H9c2 心肌细胞中的凋亡和自噬，而体内恢复 miR-342-3p 的表达增强了 AMI-Exo 的修复功能。进一步的机制研究表明，SOX6 和 TFEB 基因是 miR-342-3p 的两个直接和功能靶标。总之，在 AMI 后早期恢复期，血浆外泌体中失调的 miR-342-3p 可能与其受损的心脏保护潜能有关。miR-342-3p 通过分别靶向 SOX6 和 TFEB 抑制心肌细胞凋亡和自噬，从而促进外泌体介导的心脏修复。我们的工作为血浆外泌体在 AMI 后心脏自然修复过程中的作用提供了新的见解，并为治疗方法的发展提供了建议。
