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Journal of Lipid Research, Vol. 45, 272-280, February 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

ApoB-containing lipoproteins in apoE-deficient mice are not metabolized by the class B scavenger receptor BI

Nancy R. Webb^a,b, Maria C. de Beer^a,b, Frederick C. de Beer^a,b and Deneys R. van der Westhuyzen^a,b

^a Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536
^b Department of Veterans Affairs Medical Center, Lexington, KY 40511

To whom correspondence should be addressed. e-mail: nrwebb1{at}uky.edu

The scavenger receptor class B type I (SR-BI) recognizes a broad variety of lipoprotein ligands, including HDL, LDL, and oxidized LDL. In this study, we investigated whether SR-BI plays a role in the metabolism of cholesterol-rich lipoprotein remnants that accumulate in apolipoprotein E (apoE)^-/- mice. These particles have an unusual apolipoprotein composition compared with conventional VLDL and LDL, containing mostly apoB-48 as well as substantial amounts of apoA-I and apoA-IV. To study SR-BI activity in vivo, the receptor was overexpressed in apoE^-/- mice by adenoviral vector-mediated gene transfer. An 10-fold increase in liver SR-BI expression resulted in no detectable alterations in VLDL-sized particles and a modest depletion of cholesterol in intermediate density lipoprotein/LDL-sized lipoprotein particles. This decrease was not attributable to altered secretion of apoB-containing lipoproteins in SR-BI-overexpressing mice. To directly assess whether SR-BI metabolizes apoE^-/- mouse lipoprotein remnants, in vitro assays were performed in both CHO cells and primary hepatocytes expressing high levels of SR-BI. This analysis showed a remarkable deficiency of these particles to serve as substrates for selective lipid uptake, despite high-affinity, high-capacity binding to SR-BI.

Taken together, these data establish that SR-BI does not play a direct role in the metabolism of apoE^-/- mouse lipoprotein remnants.

Abbreviations: apoE, apolipoprotein E; CE, cholesteryl ester; CEt, cholesteryl ether; LDLR, LDL receptor; SR-BI, scavenger receptor class B type I

Supplementary key words selective lipid uptake • lipoprotein metabolism • adenoviral vector • hepatocytes • apolipoprotein B • apolipoprotein E

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