Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration.

Angiotensin II (Ang II) plays a central role in vascular smooth muscle cell (VSMC) proliferation and migration, being key to regulate vascular function and promote vascular remodeling in cardiovascular diseases. We recently showed that miR-31-5p promoted oxidative stress in spontaneously hypertensive rats. In this study, we aim to investigate whether miR-31-5p and fibronectin type III domain-containing 5 (FNDC5) contribute to Ang II-induced VSMC proliferation and migration. Experiments were performed in primary VSMCs of wide-type (WT) and FNDC5 mice as well as the rat A7r5 cell line. We found that Ang II increased miR-31-5p level, reduced FNDC5 expression and stimulated VSMC proliferation and migration, which were aggravated by miR-31-5p mimic, and prevented by miR-31-5p inhibitor in VSMCs. The Ang II-induced VSMC proliferation were prevented by exogenous FNDC5 in both WT and FNDC5 mice, while the effects were more significant in FNDC5 mice. Furthermore, exogenous FNDC5 reversed the effects of miR-31-5p mimic on VSMC proliferation and migration in Ang II-treated VSMCs. Meanwhile, FNDC5 deficiency prevented the effects of miR-31-5p inhibitor on VSMC proliferation and migration in Ang II-treated VSMCs. In conclusion, our findings demonstrate that the miR-31-5p upregulation and the following FNDC5 downregulation contribute to Ang II-induced VSMC proliferation and migration.