Abstract
Extracellular vesicles derived from human umbilical cord mesenchymal stem cells stimulate angiogenesis in myocardial infarction via the microRNA-423-5p/EFNA3 axis
- Department of Cardiovascular Medicine, Ankang Central Hospital, Ankang City, China
Introduction:
Myocardial infarction (MI) is a severe disease that has an association with angiogenesis dysfunction.
Aim:
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.
Material and methods:
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.
Results:
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.
Conclusions:
EVs promote in vivo angiogenesis in MI rats via the miR-423-5p/EFNA3 axis, thus improving cardiac repair.
Keywords
myocardial infarction, human umbilical cord mesenchymal stem cells, extracellular vesicles, microRNA-423-5p, EFNA3, angiogenesis
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