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Papers In Press, published online ahead of print August 1, 2005
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Department of Lipid Metabolism, JM/HNRCA at Tufts Univaresity, Boston, MA 02111
Corresponding Author: bela.asztalos{at}tufts.edu
Objective: To evaluate the associations of individual apolipoprotein (apo)A-I-containing HDL subpopulation levels with ABCA1- and SR-BI-mediated cellular cholesterol efflux. Methods: HDL subpopulations were measured by non-denaturing 2-dimensional gel-electrophoresis from 105 male subjects selected with various levels of apoA-I in preß-1, a-1, and a-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. Results: 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, a-2 particles (p=0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with a-2 (p=0.0004), a-1 (p=0.0030), preß-1 (p=0.0056) and a-3 (p=0.0127) HDL particles. Conclusions: 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 SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size.
Revised on July 18, 2005
Accepted on July 21, 2005
Differential effects of HDL subpopulations on cellular ABCA1- and SRB1-mediated cholesterol efflux
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