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Originally published In Press as doi:10.1194/jlr.M500187-JLR200 on August 1, 2005

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Journal of Lipid Research, Vol. 46, 2246-2253, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux

Bela F. Asztalos1,*, Margarita de la Llera-Moya{dagger}, Gerard E. Dallal*, Katalin V. Horvath*, Ernst J. Schaefer* and George H. Rothblat{dagger}

* Lipid Metabolism Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA
{dagger} Gastrointestinal/Nutrition Division, Children's Hospital of Philadelphia, Philadelphia, PA

Published, JLR Papers in Press, August 1, 2005. DOI 10.1194/jlr.M500187-JLR200

1 To whom correspondence should be addressed. e-mail: bela.asztalos{at}tufts.edu

Our objective was to evaluate the associations of individual apolipoprotein A-I (apoA-I)-containing HDL subpopulation levels with ABCA1- and scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing two-dimensional gel electrophoresis from 105 male subjects selected with various levels of apoA-I in preß-1, {alpha}-1, and {alpha}-3 HDL particles. ApoB-containing lipoprotein-depleted serum was incubated with [3H]cholesterol-labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1-mediated efflux. SR-BI-mediated efflux was determined using cholesterol-labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1-mediated efflux: small, lipid-poor preß-1 particles (P = 0.0022) and intermediate-sized {alpha}-2 particles (P = 0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with {alpha}-2 (P = 0.0004), {alpha}-1 (P = 0.0030), preß-1 (P = 0.0056), and {alpha}-3 (P = 0.0127) HDL particles.

These data demonstrate that the small, lipid-poor preß-1 HDL has the strongest association with ABCA1-mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size.

Supplementary key words apolipoprotein A-I • reverse cholesterol transport • ATP binding cassette transporter A1 • scavenger receptor class B type I • high density lipoprotein


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