In vitro study of the cytotoxicity of isolated oxidized lipid low-density lipoproteins fractions in human endothelial cells: Relationship with the glutathione status and cell morphology

Toxic effects of oxidized lipid compounds contained in oxidized LDL to endo thelial cells are involved in the pathogenesis of atherosclerosis. Glutathi one (GSH) plays an important role in the redox status of the cell and in th e protective effect against oxidant injuries. However, little is known abou t the respective effect of these different oxidized lipid compounds toward cytotoxicity and GSH status of the cell. In this report, we isolated by hig h-performance liquid chromatography oxidized lipid compounds from low-densi ty lipoproteins (LDL) oxidized by copper and we examined their effects on c ultured endothelial cells. Cytotoxicity and GSH status were determined afte r incubation of endothelial cells with crude LDL or isolated lipid fraction s derived from cholesterol, phospholipids, or cholesteryl esters, Their eff ects on cell morphology were also assessed. Oxidized lipids coming from cho lesteryl esters (hydroperoxides or short-chain polar derivatives) induced a slight but significant GSH depletion without inducing cytotoxicity. The sa me species coming from phospholipids induced a more pronounced GSH depletio n and a cytotoxic effect which is only present for the more polar compounds (short-chain polar derivatives) and corresponding to a total GSH depletion . In contrast, fractions containing oxysterols had a larger cytotoxic effec t than their effect on GSH depletion suggesting that their cytotoxic effect s are mediated by a GSH-independent pathway. AU together, these data sugges t that LDL-associated oxidized lipids present in copper-oxidized LDL exert cytotoxicity by an additional or synergistic effect on GSH depletion, but a lso by another mechanism independent of the redox status of the cell. (C) 2 000 Elsevier Science Inc.