Extracellular vesicles derived from human umbilical cord mesenchymal stem cells stimulate angiogenesis in myocardial infarction via the microRNA-423-5p/EFNA3 axis.

Abstract

Myocardial infarction (MI) is a severe disease that has an association with angiogenesis dysfunction. This study explores the mechanism of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hucMSCs) affecting angiogenesis in MI via the microRNA (miR)-423-5p/EFNA3 axis. HucMSC-derived EVs (hucMSC-EVs) were isolated, extracted, and identified. EVs and human umbilical vein endothelial cells (HUVECs) were co-cultured. Migration capacity and angiogenesis ability of HUVECs were measured, and VEGF levels in cell supernatants were tested by ELISA. In-vivo rat MI models were established, and hucMSC-EVs were injected into the MI rat heart-infarcted area. Cardiac function, capillary density, and the degree of myocardial fibrosis were observed. HUVEC migration and angiogenesis were promoted by hucMSC-EVs, and more significantly enhanced by hucMSC-EVs containing miR-423-5p. Furthermore, miR-423-5p inhibited EFNA3 expression and EFNA3 overexpression reversed the promoting effects of EVs on HUVEC migration and angiogenesis. miR-423-5p expression was elevated and EFNA3 expression was reduced in myocardial tissues of MI rats after EV treatment. Both EVs and EVs containing miR-423-5p could improve cardiac function, reduce the area of fibrosis, and promote angiogenesis, improving cardiac repair. EVs promote in vivo angiogenesis in MI rats via the miR-423-5p/EFNA3 axis, thus improving cardiac repair.