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Journal of Lipid Research, Vol 34, 295-308, Copyright © 1993 by Lipid Research, Inc.
S Dejager, E Bruckert and MJ Chapman
Patients presenting combined hyperlipidemia (CHL) display an elevated risk
of coronary heart disease. The atherogenic lipoprotein particles implicated
in this disorder remain ill defined. We determined the qualitative and
quantitative characteristics of the density distribution of low density
lipoprotein (LDL) particle subspecies in nine subjects defined
phenotypically as presenting CHL, and under strict dietary control. Seven
CHL patients possessed familial antecedents of premature coronary heart
disease; none were E2E2 homozygotes. Five LDL subspecies were isolated by
density gradient ultracentrifugation in the density range 1.019-1.063 g/ml.
In all patients, the LDL profile was skewed towards the dense subspecies
(LDL- 4, d 1.039-1.050 g/ml and LDL-5, d 1.050-1.063 g/ml), representing
47% of total LDL mass; by contrast, these subspecies accounted for only 30%
of LDL mass in five normolipidemic subjects (P < 0.01). In addition,
plasma LDL mass concentrations were some twofold higher in CHL patients as
compared to normolipidemic subjects. The % mass of LDL-4 was positively
correlated with plasma triglyceride and apoB levels. LDL-2 and LDL-3 in CHL
patients were triglyceride-enriched (11.9 and 7.2%, respectively) as
compared to the corresponding subspecies in normolipidemic subjects (6.6
and 3.7%, respectively; P < 0.05 in each case). LDL particle size
decreased with increase in density in both groups; however, significant
differences were found between corresponding LDL subspecies (LDL-1, -3, -4,
and -5) in CHL patients and normolipidemic subjects, a finding suggestive
of dissimilar molecular organization, despite correspondence in hydrated
density. The copper-induced oxidative modification of LDL subspecies was
assessed by determination of conjugated diene formation. In both groups,
LDL-5 was distinct in exhibiting a marked diminution in oxidative
resistance as indicated by a significant reduction (P < 0.01) in mean
lag time. The oxidative susceptibility of LDL subspecies in both groups was
independent of vitamin E content when expressed as the ratio vitamin E/LDL
mass, although dense LDL in CHL patients tended to be deficient in this
antioxidant. The diminished oxidative resistance of dense LDL subspecies
could not be accounted for by enrichment in polyunsaturated fatty acids in
either group. These studies suggest that in consequence of their elevated
circulating concentration and diminished oxidative resistance, dense LDL
subspecies represent putative atherogenic subspecies in combined
hyperlipidemia.
ARTICLES
Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia
Lipoprotein and Atherogenesis Research Unit, Institut National de la Sante et de la Recherche Medicale, INSERM U.321, Hopital de la Pitie, Paris, France.
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 B. Lamarche, A. Tchernof, S. Moorjani, B. Cantin, G. R. Dagenais, P. J. Lupien, and J.-P. Despres Small, Dense Low-Density Lipoprotein Particles as a Predictor of the Risk of Ischemic Heart Disease in Men: Prospective Results From the Quebec Cardiovascular Study Circulation, January 7, 1997; 95(1): 69 - 75. [Abstract] [Full Text]
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R. Prassl, J. M. Chapman, F. Nigon, M. Sara, S. Eschenburg, C. Betzel, A. Saxena, and P. Laggner Crystallization and Preliminary X-ray Analysis of a Low Density Lipoprotein from Human Plasma J. Biol. Chem., November 15, 1996; 271(46): 28731 - 28733. [Abstract] [Full Text] [PDF]
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A. D. Tselepis, C. Dentan, S.-A. P. Karabina, M. J. Chapman, and E. Ninio PAF-Degrading Acetylhydrolase Is Preferentially Associated With Dense LDL and VHDL-1 in Human Plasma : Catalytic Characteristics and Relation to the Monocyte-Derived Enzyme Arterioscler. Thromb. Vasc. Biol., October 1, 1995; 15(10): 1764 - 1773. [Abstract] [Full Text]
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P. Lesnik, C. Dentan, A. Vonica, M. Moreau, and M. J. Chapman Tissue Factor Pathway Inhibitor Activity Associated With LDL Is Inactivated by Cell- and Copper-Mediated Oxidation Arterioscler. Thromb. Vasc. Biol., August 1, 1995; 15(8): 1121 - 1130. [Abstract] [Full Text]
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J. E. Hokanson, R. M. Krauss, J. J. Albers, M. A. Austin, and J. D. Brunzell LDL Physical and Chemical Properties in Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., April 1, 1995; 15(4): 452 - 459. [Abstract] [Full Text]
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