Exosomal microRNA-1246 from human umbilical cord mesenchymal stem cells potentiates myocardial angiogenesis in chronic heart failure.

microRNAs (miRNAs) are of importance to chronic heart failure (CHF). However, the relevance of the exosomal miRNAs produced during CHF remains unknown. Our purpose here was to examine the relevance of exosomal microRNA-1246 (miR-1246) released from human umbilical cord mesenchymal stem cell (hucMSC) during CHF and the mechanism of action. Cardiac function, myocardial infarction area, apoptosis, and angiogenesis were all evaluated in a CHF rat model following treatment with hucMSC-derived exosomes (hucMSC-Exos). H9C2 and human umbilical vascular endothelial cells (HUVECs) were subjected to oxygen and glucose deprivation and exosome treatment to quantify the cell proliferation and apoptosis in H9C2 cells and the tube formation capacity of the HUVECs. A dual-luciferase activity reporter assay was conducted to validate the interaction between miR-1246 and serine protease 23 (PRSS23). HucMSCs treatment led to a reduction in H9C2 apoptosis and an increase in HUVEC angiogenesis, which were mitigated when hucMSCs were treated with a miR-1246 inhibitor. We also confirmed that PRSS23 is a putative target of miR-1246 and that miR-1246 attenuated hypoxia-induced myocardial tissue damage by targeting PRSS23 and inhibiting the activation of the Snail/alpha-smooth muscle actin signaling. Our findings suggest that exosomal miR-1246 from hucMSCs protects the heart from failure by targeting PRSS23.