IMPAIRED CELLULAR CHOLESTEROL EFFLUX BY OXYSTEROL-ENRICHED HIGH-DENSITY-LIPOPROTEINS

One of the proposed antiatherogenicity role of high-density lipoprotei ns (HDL) is believed to stimulate removal of cholesterol from the peri pheral 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 m odified HDL3 resulted in a significantly reduced efflux of labeled cho lesterol from preloaded macrophages (P388D(1) cell line). Analysis of lipid composition of Ox-HDL3 by gas chromatography revealed the presen ce of oxysterols (OS). Enrichment of native HDL3 with oxysterols resul ted in a reduced capacity to stimulate cholesterol efflux. The reduced ability of OS-enriched HDL3 to elicit cholesterol efflux may contribu te to cellular cholesterol accumulation and subsequently to atheroscle rosis. (C) 1997 Elsevier Science Inc.