Impaired cellular cholesterol efflux by oxysterol-enriched high density lipoproteins.
One of the proposed antiatherogenicity role of high-density lipoproteins (HDL) is believed to stimulate removal of cholesterol from the peripheral cells back to the liver for excretion. We have investigated the effects of oxidation-related modifications of HDL on their ability to stimulate cholesterol efflux from cultured cells. Human HDL (HDL3, 1.13 < d < 1.21 g/ml) have been modified either by malondialdehyde or by copper-mediated oxidation (Ox-HDL3). Compared with native HDL3, the modified HDL3 resulted in a significantly reduced efflux of labeled cholesterol from preloaded macrophages (P388D1 cell line). Analysis of lipid composition of Ox-HDL3 by gas chromatography revealed the presence of oxysterols (OS). Enrichment of native HDL3 with oxysterols resulted in a reduced capacity to stimulate cholesterol efflux. The reduced ability of OS-enriched HDL3 to elicit cholesterol efflux may contribute to cellular cholesterol accumulation and subsequently to atherosclerosis.
Gesquière
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L
INSERM CJF 93-10, Laboratoire de Biochimie des Lipoprotéines, Université de Bourgogne, Dijon, France.
Loreau
N
N
Blache
D
D
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002849:Chromatography, Gas; D003300:Copper / Q000494:pharmacology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008315:Malondialdehyde / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008075:Lipoproteins, HDL; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D003300:Copper; D002784:Cholesterol; C003001:7-ketocholesterol