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J Biol Chem, Vol. 273, Issue 10, 5599-5606, March 6, 1998
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From the We recently reported that the rate of efflux of
cholesterol from cells to high density lipoprotein (HDL) was related to
the expression level of scavenger receptor class B type I (SR-BI). Moreover, the expression of this receptor in atheromatous arteries raises the possibility that SR-BI mediates cholesterol efflux in the
arterial wall (Ji, Y., Jian, B., Wang, N., Sun, Y., de la Llera Moya,
M., Phillips, M. C., Rothblat, G. H., Swaney, J. B., and
Tall, A. R. (1997) J. Biol. Chem. 272, 20982-20985). In this paper we describe studies that suggest that the
presence of phospholipid on acceptor particles plays an important role in modulating interaction with the SR-BI. Specifically, enrichment of
serum with phospholipid resulted in marked stimulation of cholesterol efflux from cells that had higher levels of SR-BI expression, like
Fu5AH or Y1-BS1 cells, and little or no stimulation in cells with low
SR-BI levels, such as Y-1 cells. Stimulation of efflux by phospholipid
enrichment was also a function of SR-BI levels in Chinese hamster ovary
cells transfected with the SR-BI gene. Efflux to protein-free vesicles
prepared with 1-palmitoyl-2-oleoylphosphatidyl-choline also
correlated with SR-BI levels, suggesting that phospholipid, as
well as protein, influences the interaction that results in cholesterol
efflux. By contrast, cholesterol efflux from a non-cell donor showed no
stimulation consequent to phospholipid enrichment of the serum
acceptor. These results may help to explain observations in the
literature that document an increased risk of atherosclerosis in
patients with depressed levels of HDL phospholipid even in the face of
normal HDL cholesterol levels.
Department of Biochemistry, Allegheny
University of the Health Sciences, Philadelphia, Pennsylvania 19129 and
§ Division of Molecular Medicine, Department of Medicine,
Columbia University, New York, New York 10032
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