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Journal of Lipid Research, Vol. 43, 1421-1428, September 2002
Copyright © 2002 by Lipid Research, Inc.
Overexpression of SR-BI by adenoviral vector promotes clearance of apoA-I, but not apoB, in human apoB transgenic mice
,**,**
* Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536
Biochemistry, University of Kentucky Medical Center, Lexington, KY 40536
Gill Heart Institute, University of Kentucky Medical Center, Lexington, KY 40536
** Department of Veterans Affairs Medical Center, Lexington, KY 40511
1 To whom correspondence should be addressed. e-mail: nrwebb1{at}pop.uky.edu
Scavenger receptor BI (SR-BI) is a multi-ligand lipoprotein receptor that mediates selective lipid uptake from HDL, and plays a central role in hepatic HDL metabolism. In this report, we investigated the extent to which SR-BI selective lipid uptake contributes to LDL metabolism. As has been reported for human LDL, mouse SR-BI expressed in transfected cells mediated selective lipid uptake from mouse LDL. However, LDL-cholesteryl oleoyl ester (CE) transfer relative to LDL-CE bound to the cell surface (fractional transfer) was 
18-fold lower compared with HDL-CE. Adenoviral vector-mediated SR-BI overexpression in livers of human apoB transgenic mice (10-fold increased expression) reduced plasma HDL-cholesterol (HDL-C) and apolipoprotein (apo)A-I concentrations to nearly undetectable levels 3 days after adenovirus infusion. Increased hepatic SR-BI expression resulted in only a modest depletion in LDL-C that was restricted to large LDL particles, and no change in steady-state concentrations of human apoB. Kinetic studies showed a 19% increase in the clearance rate of LDL-CE in mice with increased SR-BI expression, but no change in LDL apolipoprotein clearance. Quantification of hepatic uptake of LDL-CE and LDL-apolipoprotein showed selective uptake of LDL-CE in livers of human apo B transgenic mice. However, such uptake was not significantly increased in mice over-expressing SR-BI.
We conclude that SR-BI-mediated selective uptake from LDL plays a minor role in LDL metabolism in vivo.
Abbreviations: CE, cholesteryl oleoyl ester; CEt, cholesteryl oleoyl ether; CHO, Chinese hamster ovary; SR-BI, scavenger receptor class B type I
Supplementary key words scavenger receptor BI • selective uptake • apolipoprotein B • transfected cells • low density lipoprotein receptor • transgenic mice • adenoviral vector
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