MiR-18a-5p inhibits endothelial–mesenchymal transition and cardiac fibrosis through the Notch2 pathway

Abstract

Hyperglycemia plays a crucial role in the pathogenesis of diabetic complications; however, the mechanisms underlying diabetic cardiac fibrosis remain unclear. Endothelial cells are known to contribute to cardiac fibrosis through endothelial–mesenchymal transition (EndMT) under high glucose stimulation. Here we investigated the expression of miR-18a-5p and examined its functional role in human aortic valvular endothelial cells (HAVECs). Using HAVECs, we revealed that miR-18a-5p regulated high glucose-induced EndMT. Moreover, high glucose levels induced Notch2 expression, which promoted EndMT, resulting in the downregulation of vascular endothelial cadherin and CD31 and upregulation of fibroblast-specific protein-1, α-smooth muscle actin, fibronectin, and vimentin. Furthermore, Notch2 was identified as a target of miR-18a-5p. Our data showed that the overexpression of miR-18a-5p could downregulate Notch2 expression and subsequently suppress EndMT. In conclusion, our findings demonstrated that miR-18a-5p/Notch2 signaling pathway participates in the regulation of high glucose-induced EndMT, and may act as a novel promising target for myocardial fibrosis in diabetic cardiomyopathy.