Abstract
Bone marrow-mesenchymal stem cell (BM-MSC) therapy improves the recovery of cardiac function after myocardial infarction (MI); however, the underlying molecular mechanisms are not completely understood. Recent studies have shown that microRNAs (miRNAs) modulate the pathophysiology of cardiovascular diseases. Here, we investigated the mechanisms underlying the effects of BM-MSC-derived paracrine factors and cardiac miRNAs on myocardial regeneration after MI. In our study, MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. BM-MSCs transplanted in infarcted rats significantly downregulated the expression of miRNA-23a and miRNA-92a and inhibited apoptosis in the myocardium. An in vitro experiment showed that supernatant from BM-MSCs cultured under hypoxia contained higher levels of vascular endothelial growth factor (VEGF) than that from BM-MSCs under normoxia. In addition, inhibition of miRNA-23a and miRNA-92a reduced cardiac apoptosis. Moreover, the VEGF-containing BM-MSC supernatant inhibited miRNA-23a and miRNA-92a expression and reduced apoptotic signaling in cardiomyocytes under hypoxia. These effects were inhibited when the supernatant was treated with neutralizing antibodies against VEGF. Our results indicate that the paracrine factor, VEGF, derived from transplanted BM-MSCs, regulated the expression of miRNAs such as miRNA-23a and miRNA-92a and exerted anti-apoptotic effects in cardiomyocytes after MI.