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Journal of Lipid Research, Vol. 48, 177-184, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic

Hsin-hung Chen^*, Brian D. Hosken^*, Max Huang^*, John W. Gaubatz^*, Christine L. Myers, Ronald D. Macfarlane, Henry J. Pownall^* and Chao-yuh Yang^1,*

^* Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030
Cardiovascular Research Group, Department of Chemistry, Texas A&M University, College Station, TX 77843

Published, JLR Papers in Press, October 2, 2006.

¹ To whom correspondence should be addressed. e-mail: cyang{at}bcm.tmc.edu

ABSTRACT

A highly electronegative fraction of human plasma LDLs, designated L5, has distinctive biological activity that includes induction of apoptosis in bovine aortic endothelial cells (BAECs). This study was performed to identify a relationship between LDL density, electronegativity, and biological activity, namely, the induction of apoptosis in BAECs. Plasma LDLs from normolipidemic subjects and homozygotic familial hypercholesterolemia subjects were separated into five subfractions, with increasing electronegativity from L1 to L5, and into seven subfractions according to increasing density, D1 to D7. L1 to L5 were also separated according to density, and D1 to D7 were separated according to charge. The density profiles of L1 to L5 were similar (maximum density = 1.030 ± 0.002 g/ml). Induction of apoptosis by all seven density subfractions was confined to the highly electronegative fraction, L5, and within each density subfraction the magnitude of apoptosis correlated with the L5 content. Electronegative LDL is heterogeneous with respect to density and composition, and induction of apoptosis is more strongly associated with LDL electronegativity than with LDL size or density.

Supplementary key words low density lipoprotein • apoptosis • low density lipoprotein dense subfractions • atherosclerosis

Abbreviations: apoB-100, apolipoprotein B-100; BAEC, bovine aortic endothelial cell; CHD, coronary heart disease; EC, endothelial cell; EDGUC, equilibrium density gradient ultracentrifugation; FH, familial hypercholesterolemic; LDL^–, electronegative low density lipoprotein; NaBiEDTA, sodium salt of a bismuth-EDTA complex; NBD C₆-ceramide, 6-{[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoyl}; NL, normolipidemic; REM, relative electrophoretic mobility; SEC, size-exclusion chromatography; sdLDL, small, dense low density lipoprotein

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