Coronary artery disease (CAD) is one of the main causes of hospitalization worldwide and has high morbidity. It has previously been demonstrated that stem cells serve an important role in improving myocardial function. MicroRNA (miRNA)-146a downregulation has been reported to inhibit vascular smooth muscle cell apoptosis in a rat model of coronary heart disease. The aim of the present study was to investigate the mechanisms underlying the effects of endothelial stem cell (ESC)-derived paracrine factors and cardiac miRNAs in CAD. Acute myocardial infarction was induced in 20 rats. Autologous ESCs (n=10; experimental group) or PBS (n=10; control group) were injected in the border zone. Reverse transcription-quantitative polymerase chain reaction, ELISA and immunohistochemistry assays were performed to analyze the therapeutic effects of ESCs in rats with coronary heart disease rats. Serum interleukin (IL)-1, IL-17 and tumor necrosis factor-α were reduced in the experimental group compared with control rats, as was the number of circulating proatherogenic cells. The results demonstrated that ESC transplantation markedly downregulated miRNA-146a expression and decreased apoptosis in the myocardium compared with the control group. Rats in the experimental group also had higher levels of vascular endothelial growth factor compared with the control group. In addition, it was demonstrated that miRNA-146 knockdown reduced cardiac apoptosis and increased VEGF expression. Furthermore, the infarct area in the border zone or rats with CAD was reduced in the experimental group compared with the control group. In conclusion, these results suggest that ESC transplantation may improve cardiac function via downregulating miR-146a, which may be have potential as a treatment for CAD.
Keywords: apoptosis; coronary heart disease; endothelial stem cells; microRNA-146a; vascular endothelial growth factor.