MiR-133a-3p transferred by circulating microvesicles derived from myocardial ischemic preconditioning protects cardiomyocytes against hypoxia/reoxygenation injury

Abstract

Background Microvesicles (MVs) are submicron membrane vesicles as mediators of intercellular communication. The aim of our study was to investigate protective mechanism of circulating MVs derived from ischemic preconditioning (IPC-MVs) on myocardial I/R injury. Results Administration of IPC-MVs reduced infarct size and activity of lactate dehydrogenase (LDH) in myocardial I/R injury in vivo. Meanwhile, IPC-MVs could increase cell viability and reduce LDH activity in hypoxia/reoxygenation (H/R) injured H9c2 cells in vitro. Microarray analysis demonstrated that miR-133a-3p expression in IPC-MVs increased apparently compared with Sham-MVs. We found that miR-133a-3p increased cell viability, decreased LDH activity and apoptosis , as well as suppressed H/R-induced endoplasmic reticulum stress (ERS). MVs induced by hypoxic preconditioning enriched with FAM-miR-133a-3p allowed the transfer of miR-133a-3p to target cells. In addition, miR-133a-3p was significantly increased in H/R injured H9c2 cells by treatment with IPC-MVs. Epidermal growth factor receptor (EGFR) is a target gene of miR-133a-3p. AG1478 (EGFR inhibitor) significantly increased cell viability, decreased LDH activity and ERS-induced apoptosis in H9c2 cells under H/R injury. Conclusions The findings of this study showed that IPC-MVs exerted cardioprotective effects by transferring miR-133a-3p into H/R injured cardiomyocytes targeting EGFR, thus attenuating ERS-induced apoptosis. MiR-133a-3p transferred by IPC-MVs may provide a novel therapy for myocardial I/R injury.