Overexpression of Human Superoxide Dismutase Inhibits Oxidation of Low-Density Lipoprotein by Endothelial Cells

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Abstract
—Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O 2 .− ) and oxidize LDL in vitro; however, the role of O 2 .− in endothelial cell–induced LDL oxidation is unclear. Incubation of human LDL (200 μg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5±1.1 versus 6.3±0.2 [mean±SEM] nmol malondialdehyde/mg LDL protein, respectively; P 2 .− release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of O 2 .− contributes to endothelial cell–induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.