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.
Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.
Bhadra
S
S
Department of Internal Medicine, University of Cincinnati Medical Center, Ohio 45267.
Arshad
M A
MA
Rymaszewski
Z
Z
Norman
E
E
Wherley
R
R
Subbiah
M T
MT
D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003300:Copper / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D015227:Lipid Peroxidation; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D012867:Skin / Q000378:metabolism; D014471:Umbilical Veins
D008078:Cholesterol, LDL; D009829:Oleic Acids; D019301:Oleic Acid; D003300:Copper; D002784:Cholesterol