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Journal of Lipid Research, Vol 32, 1741-1753, Copyright © 1991 by Lipid Research, Inc.
F Nigon, P Lesnik, M Rouis and MJ Chapman
The low density lipoproteins (LDL) of human plasma consist of a series of
discrete particle subspecies of distinct physicochemical, immunological,
and hydrodynamic properties. Such structural differences are intimately
linked to the metabolic heterogeneity of circulating LDL in vivo. The
current studies were designed to evaluate and compare the interaction of
discrete LDL subspecies from normolipidemic subjects with the LDL receptor.
Plasma LDL of d 1.019-1.063 g/ml from healthy males were fractionated into
15 subspecies of defined physicochemical characteristics by isopycnic
density gradient ultracentrifugation as described earlier (Chapman et al.,
J. Lipid Res. 1988. 29: 442-458). The major LDL subspecies, LDL-5 to
LDL-10, exhibited an overall range in density from 1.0244 to 1.0435 g/ml;
individual subspecies increased in density by increments of 0.027 (LDL-5),
0.026 (LDL-6), 0.030 (LDL- 7), 0.031 (LDL-8), 0.035 (LDL-9), and 0.042 g/ml
(LDL-10), respectively. Taken together, these subspecies accounted for
approximately 70% of the total mass of LDL of d 1.019-1.063 g/ml; their
cholesterol: protein ratios decreased from 1.70 to 1.12 and particle size
from 275 to 260 A with increase in density. ApoB-100 was the unique protein
component in subspecies 5-8, with trace amounts (less than 0.2% of apoLDL)
of both apoA-I and apoE in subspecies 9 and 10. The interaction of
individual LDL subspecies with the LDL receptor on cultured human U-937
monocyte-like cells was compared by determining receptor binding affinities
at 4 degrees C. Scatchard analysis of specific binding curves demonstrated
a single class of binding site for each subspecies. The lowest dissociation
constants were displayed by LDL subspecies 6 (Kd 5.71 nM), 7 (Kd 5.24 nM)
and 8 (Kd 4.67 nM), while subspecies 5, 9, and 10 displayed significantly
higher Kd values (8.35, 7.20, and 6.87 nM, respectively). Competitive
displacement studies at 4 degrees C, in which unlabeled subspecies from the
same gradient series competed for binding with 125I-labeled LDL subspecies,
confirmed the relative binding affinities of these subspecies. As the
hydrophobic lipid core of LDL undergoes a thermotropic transition at
approximately 37 degrees C, which may in turn influence the surface
structure of the particle, internalization and degradation studies were
performed at 37 degrees C. No effect of temperature was detectable; again,
LDL subspecies at each extreme of the density distribution (LDL-5 and LDL-
10) displayed significantly lower binding affinities for the LDL receptor
than that from the peak region (LDL-7).(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor
INSERM Unite 321, Hopital de la Pitie, Paris, France.
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B. Chappey, B. Beyssen, E. Foos, F. Ledru, J. L. Guermonprez, J. C. Gaux, and I. Myara Sialic Acid Content of LDL in Coronary Artery Disease: No Evidence of Desialylation in Subjects With Coronary Stenosis and Increased Levels in Subjects With Extensive Atherosclerosis and Acute Myocardial Infarction : Relation Between Desialylation and In Vitro Peroxidation Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 876 - 883. [Abstract] [Full Text] [PDF]
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C. M. Barbagallo, G. A. Levine, P. J. Blanche, B. Y. Ishida, and R. M. Krauss Influence of ApoE Content on Receptor Binding of Large, Buoyant LDL in Subjects With Different LDL Subclass Phenotypes Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 466 - 472. [Abstract] [Full Text] [PDF]
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T. S. Lassel, M. Guerin, S. Auboiron, M. J. Chapman, and B. Guy-Grand Preferential Cholesteryl Ester Acceptors Among Triglyceride-Rich Lipoproteins During Alimentary Lipemia in Normolipidemic Subjects Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 65 - 74. [Abstract] [Full Text] [PDF]
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C. J. Packard and J. Shepherd Lipoprotein Heterogeneity and Apolipoprotein B Metabolism Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3542 - 3556. [Abstract] [Full Text]
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P. Lesnik, C. Dachet, L. Petit, M. Moreau, S. Griglio, P. Brudi, and M. J. Chapman Impact of a Combination of a Calcium Antagonist and a ß-Blocker on Cell- and Copper-Mediated Oxidation of LDL and on the Accumulation and Efflux of Cholesterol in Human Macrophages and Murine J774 Cells Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 979 - 988. [Abstract] [Full Text]
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S. Goulinet and M. J. Chapman Plasma LDL and HDL Subspecies Are Heterogenous in Particle Content of Tocopherols and Oxygenated and Hydrocarbon Carotenoids: Relevance to Oxidative Resistance and Atherogenesis Arterioscler Thromb Vasc Biol, April 1, 1997; 17(4): 786 - 796. [Abstract] [Full Text]
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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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C. D. Gardner, S. P. Fortmann, and R. M. Krauss Association of Small Low-Density Lipoprotein Particles With the Incidence of Coronary Artery Disease in Men and Women JAMA, September 18, 1996; 276(11): 875 - 881. [Abstract] [PDF]
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M. Guerin, E. Bruckert, P. J. Dolphin, G. Turpin, and M. J. Chapman Fenofibrate Reduces Plasma Cholesteryl Ester Transfer From HDL to VLDL and Normalizes the Atherogenic, Dense LDL Profile in Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, June 1, 1996; 16(6): 763 - 772. [Abstract] [Full Text]
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H. Campos, K. S. Arnold, M. E. Balestra, T. L. Innerarity, and R. M. Krauss Differences in Receptor Binding of LDL Subfractions Arterioscler Thromb Vasc Biol, June 1, 1996; 16(6): 794 - 801. [Abstract] [Full Text]
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A. Gaw, C. J. Packard, G. M. Lindsay, E. F. Murray, B. A. Griffin, M. J. Caslake, I. Colquhoun, D. J. Wheatley, A. R. Lorimer, and J. Shepherd Effects of Colestipol Alone and in Combination With Simvastatin on Apolipoprotein B Metabolism Arterioscler Thromb Vasc Biol, February 1, 1996; 16(2): 236 - 249. [Abstract] [Full Text]
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M. Halle, A. Berg, J. Keul, and M. W. Baumstark Association Between Serum Fibrinogen Concentrations and HDL and LDL Subfraction Phenotypes in Healthy Men Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 144 - 148. [Abstract] [Full Text]
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D. L. Tribble, P. M. Thiel, J. J.M. van den Berg, and R. M. Krauss Differing {alpha}-Tocopherol Oxidative Lability and Ascorbic Acid Sparing Effects in Buoyant and Dense LDL Arterioscler Thromb Vasc Biol, November 1, 1995; 15(11): 2025 - 2031. [Abstract] [Full Text]
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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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M. Guerin, P. J. Dolphin, C. Talussot, J. Gardette, F. Berthezene, and M. J. Chapman Pravastatin Modulates Cholesteryl Ester Transfer From HDL to ApoB-Containing Lipoproteins and Lipoprotein Subspecies Profile in Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, September 1, 1995; 15(9): 1359 - 1368. [Abstract] [Full Text]
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H. Campos, G. O. Roederer, S. Lussier-Cacan, J. Davignon, and R. M. Krauss Predominance of Large LDL and Reduced HDL2 Cholesterol in Normolipidemic Men With Coronary Artery Disease Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1043 - 1048. [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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V. Clavey, S. Lestavel-Delattre, C. Copin, J. M. Bard, and J. C. Fruchart Modulation of Lipoprotein B Binding to the LDL Receptor by Exogenous Lipids and Apolipoproteins CI, CII, CIII, and E Arterioscler Thromb Vasc Biol, July 1, 1995; 15(7): 963 - 971. [Abstract] [Full Text]
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