Functional modulation of antioxidant enzymes in vascular endothelial cells by glycated LDL

Reactive oxygen species (ROS) have been implicated in atherogenesis. Previous studies demonstrated that oxidized LDL (oxLDL) or glycated LDL (gly-LDL) increased the generation of superoxide from vascular endothelial cells (EC). The present study examined the effects of gly-LDL on the activation of antioxidant enzymes for the metabolism of ROS in cultured human vascular endothelial cells in comparison to oxLDL and LDL without chemical modification. Treatment with LDL, oxLDL or gly-LDL significantly increased the release of hydrogen peroxide (H2O2) from EC following 2 h of incubation and the release of superoxide after 24 h of treatment. The increased release of H2O2, but not superoxide, was normalized in EC treated with LDL or its modified forms. Elevated activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in EC were detected following a 24 h-treatment with the LDLs. The levels of GR activity and reduced/oxidized glutathione (GSH/GSSG) in EC treated with the lipoproteins were increased after 2 h, but were reduced after ≥24 h of incubation. Gly-LDL caused less increases in SOD, GPx or catalase activity, but more evident changes in GR activity and H2O2 release compared to oxLDL or LDL. The findings suggest that exposure to glucose-modified LDL altered the activities of multiple antioxidant enzymes in cultured EC, which partially normalizes the excess generation of ROS, but reduced the intracellular reservoir of GSH.