Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice

Recent studies have indicated that the scavenger receptor class B type I (S R-BI) may play an important role in the uptake of high density lipoprotein (HDL) cholesteryl ester in liver and steroidogenic tissues. To investigate the in vivo effects of liver-specific SR-BI overexpression on lipid metabol ism, we created several lines of SR-BI transgenic mice with an SR-BI genomi c construct where the SR-BI promoter region had been replaced by the apolip oprotein (apo)A-I promoter. The effect of constitutively increased SR-BI ex pression on plasma HDL and non-HDL lipoproteins and apolipoproteins was cha racterized. There was an inverse correlation between SR-BI expression and a poA-I and HDL cholesterol levels in transgenic mice fed either mouse chow o r a diet high in fat and cholesterol. An unexpected finding in the SR-BI tr ansgenic mice was the dramatic impact of the SR-BI transgene on non-HDL cho lesterol and apoB whose levels were also inversely correlated with SR-BI ex pression. Consistent with the decrease in plasma HDL and non-HDL cholestero l was an accelerated clearance of HDL, non-HDL, and their major associated apolipoproteins in the transgenics compared with control animals. These in vivo studies of the effect of SR-BI overexpression on plasma lipoproteins s upport the previously proposed hypothesis that SR-BI accelerates the metabo lism of HDL and also highlight the capacity of this receptor to participate in the metabolism of non-HDL lipoproteins.