Abstract
Scavenger receptor BI (SR-BI) binds high density lipoproteins (HDL) with high affinity and mediates the selective uptake of HDL cholesteryl ester. We examined the potential role of SR-BI in mediating cellular cholesterol efflux. In Chinese hamster ovary cells stably transfected with murine SR-BI, overexpression of SR-BI resulted in a 3-4-fold stimulation of initial cholesterol efflux rates. Efflux rates correlated with SR-BI expression in cells and HDL concentration in the medium. When incubated with synthetic cholesterol-free HDL, SR-BI-transfected cells showed approximately 3-fold increases in initial rates of efflux compared with control cells, indicating that SR-BI expression enhances net cholesterol efflux mediated by discoidal HDL. In six different cell types, including cultured macrophages, the rate of efflux of cholesterol mediated by HDL or serum was well correlated with cellular SR-BI expression level. In addition, in situ hybridization experiments revealed that SR-BI mRNA was expressed in the thickened intima of atheromatous aorta of apolipoprotein E knockout mice. Thus, SR-BI is an authentic HDL receptor mediating cellular cholesterol efflux. SR-BI may facilitate the initial steps of HDL-mediated cholesterol efflux in the arterial wall as well as later steps of reverse cholesterol transport involving uptake of HDL cholesterol in the liver.
Highlights
Scavenger receptor BI (SR-BI) binds high density lipoproteins (HDL) with high affinity and mediates the selective uptake of HDL cholesteryl ester
In this study we showed that scavenger receptor type B class I (SR-BI) overexpression markedly stimulated HDL-mediated cholesterol efflux in Chinese hamster ovary (CHO) cells
This appears to be the first demonstration of an authentic HDL receptor mediating cellular cholesterol efflux
Summary
Scavenger receptor BI (SR-BI) binds high density lipoproteins (HDL) with high affinity and mediates the selective uptake of HDL cholesteryl ester. In the present study we used SR-BI-transfected cells to evaluate a possible role of SR-BI in HDL-mediated cellular cholesterol efflux. The results, together with our finding that SR-BI mRNA is expressed in the thickened intima of atheromatous aorta, suggest a potentially important role of SR-BI in the initial steps of cholesterol efflux in the arterial wall.
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