Knockdown of growth-arrest specific transcript 5 restores oxidized low-density lipoprotein-induced impaired autophagy flux via upregulating miR-26a in human endothelial cells.

Endothelial cells injury and autophagy dysfunction play vital roles in the development of atherosclerosis. Long noncoding RNAs (lncRNAs) have been identified to participate in the pathogenesis of atherosclerosis. However, it remains largely undefined whether lncRNA growth-arrest specific transcript 5 (GAS5) could influence ox-LDL-induced autophagy dysfunction in endothelial cells. The expression levels of GAS5 and miR-26a were detected in the plasma samples of patients with atherosclerosis and oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs) by quantitative real-time PCR (qRT-PCR). Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down were performed to validate whether GAS5 could directly interact with miR-26a. The effects of ox-LDL, GAS5 or combined with miR-26a on apoptosis and autophagy were evaluated by flow cytometry analysis and western blot, respectively. Results showed that GAS5 expression was upregulated and miR-26a was downregulated in the plasma samples of patients with atherosclerosis and ox-LDL-treated HAECs. There was an interaction of reciprocal inhibition between GAS5 and miR-26a expressions in ox-LDL-treated HAECs. We further demonstrated that GAS5 directly bound to miR-26a in HAECs. Additionally, ox-LDL administration induced apoptosis and impaired autophagy flux in HAECs. Moreover, GAS5 knockdown inhibited cell apoptosis and activated autophagy flux, whereas inhibition of miR-26a reversed the effect of GAS5 in HAECs. These results revealed a novel regulatory mechanism for ox-LDL-induced impaired autophagy flux in endothelial cells.