Abstract
Cardiovascular disease (CVD) is a leading non-communicable disease with a high fatality rate worldwide. Hypertension, a common cardiovascular condition, is a significant risk factor for the development of heart failure because the activation of the renin-angiotensin system (RAS) is considered to be the major promoting reason behind myocardial fibrosis (MF). In this study, Angiotensin II (Ang II) stimulation-induced endothelial to mesenchymal transition (End-MT) in HCAECs, including the decrease of CD31 level, the increase of α-SMA, collagen I, slug, snail, and TGF-β1 levels, and the promotion of Smad2/3 phosphorylation. Meanwhile, the c-Ski level was reduced in Ang II-stimulated HCAECs. In HCAECs, Ang II-induced changes could be partially attenuated by c-Ski overexpression. miR-214-3p directly targeted c-Ski and inhibited c-Ski expression. Moreover, miR-214-3p inhibition reduced Ang II-caused End-MT in HCAECs. miR-214-3p overexpression further enhanced Ang II-induced End-MT, while c-Ski overexpression could markedly reverse the effects of miR-214-3p overexpression. In the Ang II-induced mouse cardiac hypertrophic model, Ang II-caused increase of cellular cross-sectional area and cardiac fibrosis were partially ameliorated by LV-c-Ski; when mice were co-treated with LV-c-Ski and agomir-214-3p, the beneficial effects of LV-c-Ski were reversed. In conclusion, the miR-214-3p/c-Ski axis modulated Ang II-induced End-MT in HCAECs and cardiac hypertrophy and fibrosis in the mice model.