Electronegative LDLs from familial hypercholesterolemic patients are physicochemically heterogeneous but uniformly proapoptotic.
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.
Chen
Hsin-hung
HH
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Hosken
Brian D
BD
Huang
Max
M
Gaubatz
John W
JW
Myers
Christine L
CL
Macfarlane
Ronald D
RD
Pownall
Henry J
HJ
Yang
Chao-yuh
CY
D017209:Apoptosis; D002498:Centrifugation; D004563:Electrochemistry; D004587:Electrophoresis, Agar Gel; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000473:pathology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values
D008077:Lipoproteins, LDL