MicroRNA-126 alleviates endothelial cells injury in atherosclerosis by restoring autophagic flux via inhibiting of PI3K/Akt/mTOR pathway.

MicroRNAs (miRNAs) have emerged as critical modulators of ECs function and play a vital role in the development of cardiovascular disease. Among them, miR-126 is a crucial regulator of atherosclerosis. Endothelial cells (ECs) death and autophagy have been described in cells to cope with the progression of atherosclerosis. Hence, the aim of this study is to investigate the effects of miR-126 on atherosclerosis in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs) and the potential roles of autophagy flux in these processes. Our results showed that miR-126 level was significantly reduced in ox-LDL-treated HUVECs and miR-126 overexpression induced by miR-126 mimics remarkably blocked ox-LDL-induced HUVECs injury as evidenced by the reduced cell viability, and the increased LDH release, caspase-3 activity and apoptosis ratio. In addition, ox-LDL increased LC3-II, Beclin 1, and p62 expressions in HUVECs, while these changes were nullified in the presence of treatment with bafilomycin A1 (BafA1, an inhibit autophagic flux inhibitor). However, we found that ox-LDL-induced impaired autophagy flux was recused by miR-126 mimics. Subsequently, we found that Bafi A1 pretreatment reversed the protection of miR-126 mimics against ox-LDL-induced HUVECs injury. Finally, our results showed that miR-126 mimics rescued ox-LDL-induced impaired autophagy flux through inhibiting PI3K/Akt/mTOR signaling. Taken together, our findings suggested that miR-126 alleviates ox-LDL-induced HUVECs injury through restoring autophagy flux via repressing PI3K/Akt/mTOR pathway, and further implicate the potential therapeutic targets to reverse atherosclerosis.