Plasma exosomal miR-142-3p induced by acupuncture protects against heart injury in rat with myocardial infarction by targeting Cofilin-2

Abstract Purpose The protective effects of acupuncture on myocardial injury have been identified in clinical trials, but the underlying mechanisms are still not completely understood. This study aimed to investigate the roles of exosomes induced by acupuncture in cardioprotection. Materials and methods Masson’s-trichrome staining was used to observe the size of infarcted myocardium region. Western blot was used to detect protein expression. Ultracentrifugation methods were used to isolate plasma exosomes of rats. Small RNA sequencing combined with real-time PCR were performed to analysis expression miRNAs. Bioinformatics-based analysis and dual luciferase reporter assay were used to identify target genes of miRNAs. Results Acupuncture thickened the infarct wall of the left ventricle, and inhibited apoptosis of infarcted myocardium by upregulation of Bcl-2 and down-regulation of BAX and cleaved caspase 3. These effects of acupuncture were significantly reversed by inhibiting exosome secretion. Plasma exosomes induced by acupuncture increased the viability of cardiomyocytes in H2O2-induced injury. Five miRNAs from the plasma exosomes were increased by acupuncture, and the unique miRNA (miR-142-3p) among these miRNAs was upregulated in myocardial tissue. These changes in miRNAs induced by acupuncture were similarly inversed when exosome secretion was inhibited by GW4869. Overexpressing miR-142-3p retarded oxidative damage of H9c2 by anti-apoptosis. miR-142-3p directly targeted and downregulated the expression of Cofilin-2 (CFL2). In vivo, CFL2 expression was downregulated in the infarcted myocardium by acupuncture and upregulated by GW4869 injection. Conclusion Acupuncture-derived circulating exosomes transfer cardio-protective signals to the injured heart and confer cardioprotective effects, and miR-142-3p is a major exosomal miRNA in the inhibition of myocardial apoptosis by targeting CFL2.