Protective Effect of Low Concentrations of Oxidized Low-Density Lipoprotein on Endothelial Cell Integrity

Abstract

Increasing evidence suggests that oxidized low-density lipoprotein (LDL) is associated with the development of atherosclerosis in vivo. Because endothelial injury contributes to the development of the atherogenic , we investigated the efficacy of oxidized LDL on the integrity of human umbilical cord endothelial cells (HUVECs) by analyzing cytotoxicity and cell detachment. The cellular integrity of cultured endothelial cells labeled with chromium-51. Low concentrations of oxidized LDL (25-50 micrograms protein/ml) induced morphological changes (cell elongation and formation of gaps in the cobblestone monolayer), decreased cellular cytotoxicity (by 13% compared with control). At higher concentrations of oxidized LDL (100 micrograms protein/ml), however, increases in cytotoxicity (by up to 70%) and cellular detachment (by up to 90%) were demonstrated. Native LDL, which was not oxidized in out cell system, did not induce any changes either in cytotoxicity or in cell detachment. The protective effect of low oxidized LDL concentrations against endothelial cell cytotoxicity and detachment was abolished by indomethacin (microM), indicating the involvement or prostaglandin synthesis in this protection. Our experiments suggest that oxidized LDL-induced alterations of endothelial cells involve a sequence of events leading from a non-cytotoxic protective stage to endothelial perturbation.