Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: Identification of major products and their effects

Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.

“…The same study also showed that macrophages themselves could modify LDL, which resulted in the generation of oxysterols. The oxysterols identified in oxidized LDL by other investigators show the same lipid profile as the cellular oxysterols in our study: a high concentration of 7-keto-and 7-hydroxycholesterol (3,4,35). In a recent study, we demonstrated that lipoproteins were taken up by foam cells isolated from rabbit aorta after perfusion with labeled lipoproteins.…”

ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

“…7-Ketocholesterol is a major oxysterol present in the Cu 2ϩ -treated oxLDL (52)(53)(54)(55). We have also synthesized a 22-ketocholesterol analog of oxLig-1 (i.e., 22-ketocholesteryl-9-carboxynonanoate; 9-COOH-22KC) in the same manner for synthesizing oxLig-1.…”

Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1beta in macrophages.

“…Among the constituents of oxLDL, lipid oxidation products have been suggested to have important biological effects (37)(38)(39). One group of such products are the oxysterols, generated by oxidation of cholesterol (56,57). Oxysterols are biologically active molecules which, for example, inhibit the LDL receptor function in human fibroblasts (33), reduce the LPL mRNA expression in human macrophage cells (51), and decrease the synthesis of PGI 2 in endothelial cells (58).…”