Role of superoxide in endothelial-cell modification of low-density lipoproteins.
Cultured endothelial cells and arterial smooth muscle cells have been shown to modify LDL in a way that leads to rapid uptake by macrophages. Previous studies have demonstrated that this modification involves free radical peroxidation of LDL, and that the role of the cells was to accelerate oxidation under conditions where it otherwise would occur slowly. The objective of the present study was to determine whether the modification was mediated by oxygen-derived free radicals, and whether the ability of a given cell type of line to modify LDL was related to its secretion rate of O2- or H2O2. The results showed that modification required the presence of oxygen, and could be specifically inhibited by superoxide dismutase but not by catalase or by mannitol, a hydroxyl radical scavenger. Rabbit aortic endothelial cells, rabbit arterial smooth muscle cells, monkey arterial smooth muscle cells and human skin fibroblasts were all found to modify LDL, and all of these cell types generated more O2- (superoxide dismutase-inhibitable cytochrome c reduction) than a line of bovine aortic endothelial cells that did not modify LDL. The content of superoxide dismutase and catalase was higher in bovine aortic endothelial cells than in the cell lines that modified LDL, but glutathione peroxidase levels were not different. It was concluded that cells that were capable of modifying LDL produced superoxide or a substance that could be converted to superoxide in the medium, and that superoxide was an important, though possibly indirect, mediator of the modification of LDL by cells.
Steinbrecher
U P
UP
Department of Medicine, University of British Columbia, Health Sciences Centre Hospital, Vancouver, Canada.
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D008077:Lipoproteins, LDL; D013481:Superoxides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase