Abstract
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.
Highlights
The deposition of lipids in vessel walls and the development of atheromas are thought to be opposed by removal of the cholesterol and transport back to the liver for secretion, a process known as reverse cholesterol transport [1]
It is generally accepted that efflux of cholesterol from peripheral cells to high density lipoproteins (HDL) is the first step in reverse cholesterol transport
The rate of cholesterol release varies significantly among different cell types [9, 33, 42]. This may be for several reasons, such as variability in the fluidity or cholesterol content of the plasma membrane [43], in the thickness or composition of the extracellular matrix, which might prevent the access of cholesterol acceptors to the plasma membrane, or in different expression levels of a lipoprotein receptor, such as scavenger receptor class B type I (SR-BI) [44], in the plasma membranes of different cell types
Summary
The deposition of lipids in vessel walls and the development of atheromas are thought to be opposed by removal of the cholesterol and transport back to the liver for secretion, a process known as reverse cholesterol transport [1]. Through reversible interactions with the plasma membrane, apoA-I solubilizes cholesterol and phospholipid directly from the plasma membrane and stimulates mobilization of pools of cholesterol that are readily accessible to esterification by acylCoA:cholesterol acyltransferase (16, 18 –20), an enzyme localized to the rough endoplasmic reticulum Both lipid-free apoA-I and lipid-poor pre--HDL particles presumably function effectively as natural shuttles to transport cholesterol between cells and larger ␣-HDL, since they have a relatively lower cholesterol capacity compared with ␣-HDL [1, 21]. Cholesterol Efflux to SR-BI Receptor cently, a member of the scavenger receptor family, the class B scavenger receptor SR-BI, was shown to bind HDL with high affinity [22] This receptor can bind to many other ligands, such as native LDL, modified proteins (acetylated LDL, oxidized LDL, maleylated bovine serum albumin), and anionic phospholipids [23, 24]. It has been demonstrated that in vivo the level of SR-BI is under feedback regulation in response to changes of cholesterol stores [27]
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