J. Lipid Res.
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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

Nancy R. Webb1,*,**, Maria C. de Beer*,**, Jin Yu{dagger},**, Mark S. Kindy{dagger},**, Alan Daugherty*,§, Deneys R. van der Westhuyzen*,** and Frederick C. de Beer*,**

* Departments of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536
{dagger} 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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