Oxysterol efflux from macrophage foam cells: the essential role of acceptor phospholipid.
Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic lesions and may play an active role in lesion development. For example, 7-ketocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxysterols may promote foam cell formation in atherosclerotic lesions by preventing effective clearance of excess cholesterol. ApoA-I also induces phospholipid (PL) export from foam cells and it has been suggested that cholesterol efflux is dependent upon PL association with the apolipoprotein. In the current study, the effect of oxysterol enrichment of foam cells on phospholipid efflux was measured. Export of cellular PL 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 cholesterol 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 partially by provision of PL-containing acceptors. Efflux of 7KC from both foam 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 cholesterol upon the presence of extracellular phospholipid.
Gelissen
I C
IC
Cell Biology Group, Heart Research Institute, 145 Missenden Road, Camperdown, N.S.W. 2050, Australia.
Rye
K A
KA
Brown
A J
AJ
Dean
R T
RT
Jessup
W
W
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001693:Biological Transport, Active; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007653:Ketocholesterols / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*
D016632:Apolipoprotein A-I; D007653:Ketocholesterols; D010713:Phosphatidylcholines; D010743:Phospholipids; D013261:Sterols; C003001:7-ketocholesterol