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Journal of Lipid Research, Vol. 45, 706-715, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36

Maria C. de Beer^*, Lawrence W. Castellani, Lei Cai^*, Arnold J. Stromberg, Frederick C. de Beer^* and Deneys R. van der Westhuyzen^1,*

^* Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536, and Department of Veterans Affairs Medical Center, Lexington, KY, 40511
Department of Medicine, University of California, Los Angeles, CA 90095
Department of Statistics, University of Kentucky, Lexington, KY 40506

¹ To whom correspondence should be addressed. e-mail: dvwest1{at}uky.edu

The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding specificity. SR-BI is well characterized as a HDL receptor that mediates selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL, also binds HDL and mediates selective cholesteryl ester uptake, although much less efficiently than SR-BI. Apolipoprotein A-II (apoA-II), the second most abundant HDL protein, is considered to be proatherogenic, but the underlying mechanisms are unclear. We previously showed that apoA-II modulates SR-BI-dependent binding and selective uptake of cholesteryl ester from reconstituted HDL. To investigate the effect of apoA-II in naturally occurring HDL on these processes, we compared HDL without apoA-II (from apoA-II null mice) with HDLs containing differing amounts of apoA-II (from C57BL/6 mice and transgenic mice expressing a mouse apoA-II transgene). The level of apoA-II in HDL was inversely correlated with HDL binding and selective cholesteryl ester uptake by both scavenger receptors, particularly CD36. Interestingly, for HDL lacking apoA-II, the efficiency with which CD36 mediated selective uptake reached a level similar to that of SR-BI.

These results demonstrate that apoA-II exerts a marked effect on HDL binding and selective lipid uptake by the class B scavenger receptors and establishes a potentially important relationship between apoA-II and CD36.

Abbreviations: apoA-II, apolipoprotein A-II; CE, cholesteryl ester; oxLDL, oxidized LDL; POPC, L--palmitoyloleoylphosphatidylcholine; rHDL, reconstituted HDL; SR-BI, scavenger receptor class B, type I

Supplementary key words lipoprotein metabolism • selective lipid uptake • atherosclerosis • apolipoprotein A-II • high density lipoprotein

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