Oxysterol efflux from macrophage foam cells: the essential role of acceptor phospholipid

Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic l esions and may play an active role in lesion development. For example, 7-ke tocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxy-sterols may promote foam c ell formation in atherosclerotic lesions by preventing effective clearance of excess cholesterol. ApoA-I also induces phospholipid (PL) export from fo am cells and it has been suggested that cholesterol efflux is dependent upo n pi, association with the apolipoprotein, In the current study, the effect of oxysterol enrichment of foam cells on phospholipid efflux aas measured. Export of cellular FL to apoA-I from 7KC-enriched foam cells was inhibited to the same extent as cholesterol, indicating that the reduced cholesterol export may be a consequence of a decline in the capacity of the foam cells to generate PL/ apoA-I particles capable of accepting cellular cholesterol . Incubation of foam cells with pre-formed PL/apoA-I discs increased choles terol export from 7KC-enriched cells to levels seen in 7KC-free cells. Foam cells produced by uptake of oxidized LDL, which contain similar amounts of 7KC plus other oxidation products, expressed a more profound inhibition of pL export to apoA-I, Cholesterol efflux from these cells improved only par tially by provision of PL containing acceptors. Efflux of 7KC from both foa m cell types occurred to PL/apoA-I discs but was only minimal to lipid-free apoA-I, indicating that export of this oxysterol is more dependent than ch olesterol upon the presence of extracellular phospholipid.