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Journal of Lipid Research, Vol. 45, 1666-1673, September 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Remodeling of HDL remnants generated by scavenger receptor class B type I

Nancy R. Webb^1,*, Maria C. de Beer^*, Bela F. Asztalos, Nathan Whitaker^*, Deneys R. van der Westhuyzen^* and Frederick C. de Beer^*,

^* Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY
Lipid Metabolism Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA
Department of Veterans Affairs Medical Center, Lexington, KY

¹ To whom correspondence should be addressed. e-mail: nrwebb1{at}uky.edu

Scavenger receptor class B type I (SR-BI) mediates the selective transfer of cholesteryl ester from HDL to cells. We previously established that SR-BI overexpressed in livers of apolipoprotein A-I-deficient mice processes exogenous human HDL₂ to incrementally smaller HDL particles. When mixed with normal mouse plasma either in vivo or ex vivo, SR-BI-generated HDL "remnants" rapidly remodel to form HDL-sized lipoproteins. In this study, we analyzed HDLs throughout the process of HDL remnant formation and investigated the mechanism of conversion to larger particles. Upon interacting with SR-BI, -migrating HDL₂ is initially converted to a pre-migrating particle that is ultimately processed to a smaller -migrating HDL remnant. SR-BI does not appear to generate preß-1 HDL particles. When incubated with isolated lipoprotein fractions, HDL remnants are converted to lipoprotein particles corresponding in size to the particle incubated with the HDL remnant. HDL remnant conversion is not altered in phospholipid transfer protein (PLTP)-deficient mouse plasma or by the addition of purified PLTP. Although LCAT-deficient plasma promoted only partial conversion, this deficiency was attributable to the nature of HDL particles in LCAT^–/– mice rather than to a requirement for LCAT in the remodeling process.

We conclude that HDL remnants, generated by SR-BI, are converted to larger particles by rapidly reassociating with existing HDL particles in an enzyme-independent manner.

Abbreviations: apoA-I, apolipoprotein A-I; CE, cholesteryl oleoyl ester; CETP, cholesteryl ester transfer protein; PLTP, phospholipid transfer protein; SR-BI, scavenger receptor class B type I

Supplementary key words high density lipoprotein • cholesteryl ester • selective lipid uptake

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