SCAVENGER RECEPTOR BI PROMOTES HIGH-DENSITY LIPOPROTEIN-MEDIATED CELLULAR CHOLESTEROL EFFLUX

Scavenger receptor BI (SR-EI) binds high density lipoproteins (HDL) wi th high affinity and mediates the selective uptake of HDL cholesteryl ester, We examined the potential role of SR-BI ill 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 stim ulation of initial cholesterol efflux rates. Efflux rates correlated w ith SB-BI expression in cells and HDL concentration in the medium. Whe n incubated with synthetic cholesterol-free RDL, SR-BI-transfected cel ls showed similar to 3-fold increases in initial rates of efflux compa red with control cells, indicating that SR-BI expression enhances net cholesterol efflux mediated by discoidal HDL. In six different cell ty pes, including cultured macrophages, the rate of efflux of cholesterol mediated by RDL or serum was well correlated with cellular SR-BI expr ession 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 H DL receptor mediating cellular cholesterol efflux, SR-BI may facilitat e the initial steps of HDL-mediated cholesterol efflux in the arterial wall as well as later steps of reverse cholesterol transport involvin g uptake of HDL cholesterol in the liver.