Angiopoietin-1 Protects the Endothelial Cells Against Advanced Glycation End Product Injury by Strengthening Cell Junctions and Inhibiting Cell Apoptosis

Endothelial dysfunction is a major characteristic of diabetic vasculopathy. Protection of the vascular endothelium is an essential aspect of preventing and treating diabetic vascular complications. Although Angiopoietin‐1 (Ang‐1) is an important endothelial‐specific protective factor, whether Ang‐1 protects vascular cells undergoing advanced glycation end product (AGE) injury has not been investigated. The aim of the present study was to determine the potential effects of Ang‐1 on endothelial cells after exposure to AGE. We show here that Ang‐1 prevented AGE‐induced vascular leakage by enhancing the adherens junctions between endothelial cells, and this process was mediated by the phosphorylation and membrane localization of VE‐cadherin. Furthermore, Ang‐1 also protected endothelial cells from AGE‐induced death by regulating phosphatidylinositol 3‐kinase (PI3K)/Akt‐dependent Bad phosphorylation. Our findings suggest that the novel protective mechanisms of Ang‐1 on endothelium are achieved by strengthening endothelial cell junctions and reducing endothelial cell death after AGE injury. J. Cell. Physiol. 230: 1895–1905, 2015. © 2014 Wiley Periodicals, Inc.