MicroRNA-575 suppresses angiogenesis by targetingRab5-MEK-ERK pathway in endothelial cells.

Hypertension is a major risk factor for the development of atherosclerosis. Increased carotid intima-media thickness (CIMT) is generally considered as an early marker of atherosclerosis. Recently, circulating microRNAs have been implicated both as sensitive biomarker and key regulator in development of atherosclerosis. However, the biological functions and molecular regulatory mechanisms for miR-575 on angiogenesis remain unknown. In our study, we firstly identified upregulation of circulating miR-575 in plasma of essential hypertensive patients with increased CIMT (iCIMT) compare to those patients with normal CIMT (nCIMT). Furthermore, overexpression of miR-575 in human umbilical vein endothelial cells (HUVECs) by its mimics significantly inhibited migration and proliferation as well as induction of apoptosis of HUVECs. Inhibition of miR-575 performed the reverse effects of HUVECs. We further suggested Rab5B was the downstream target of miR-575 and knockdown of Rab5B significantly inhibited migration and proliferation of HUVECs. Overexpression of Rab5B largely rescued the miR-575-mediated impairment of angiogenesis processes including cell proliferation, migration and apoptosis as well as activation of MEK-ERK signalling. Therefore, our results uncover a novel role of miR-575 in endothelial cells, implying a potential biomarker and clinical target for atherosclerosis in hypertensive patients.