Autophagy Modulates The Function Of Human Umbilical Vein Endothelial Cells Exposed To Hydrogen Peroxide Via Wnt/Beta-Catenin Signaling Pathways

Background: Oxidative stress (OS) contributes to many negative effects, producing many intermediate products that mediate cell injuries, as observed in atherosclerosis (AS). Moreover, OS promotes endothelial-tomesenchymal transition (EndMT). Autophagy and Wnt signaling pathways participate in the regulation of EndMT. Therefore, the current study examined whether autophagy and Wnt/beta-catenin signaling pathways interact in human umbilical vein endothelial cells (HUVECs) under oxidative stress conditions. Methods: Expression levels of EndMT, Wnt/beta-catenin signaling pathways, and autophagy markers in each group were measured via immunofluorescence and Western blotting. Evaluating the function of HUVECs exposed to H2O2, comprehensively, flow cytometry was used to measure apoptosis. Results: Results demonstrated that activating autophagy with Rap significantly prevented H2O2 stimulated HUVECs EndMT by downregulating alpha-smooth muscle actin (alpha-SMA) and upregulatingCD31. It also showed a significant reduction in cell apoptosis ratios. Interestingly, activation of Wnt/beta-catenin signaling pathways had similar effects to autophagy on cell apoptosis ratios. Activating Wnt/beta-catenin signaling pathways with BIO could enhance levels of EndMT in HUVECs exposed to hydrogen peroxide. Enhancement of Wnt/beta-catenin signaling pathways to EndMT could be attenuated by upregulation of autophagy. The promotion of Wnt/beta-catenin signaling pathways to apoptosis could be attenuated by activating autophagy. Autophagy modulates the function of HUVECs exposed to oxidative stress partly via interaction with Wnt/beta-catenin signaling pathways. Conclusion: Wnt/beta-catenin signaling pathways and autophagy may be used to prevent the development of atherosclerosis, as EndMT contributes to the pathobiological process of atherosclerosis.