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

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.