This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anber, V. Articles by Packard, C. J. Search for Related Content PubMed PubMed Citation Articles by Anber, V. Articles by Packard, C. J.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2507-2514.)
© 1997 American Heart Association, Inc.

Articles

Interaction of Very-Low-Density, Intermediate-Density, and Low-Density Lipoproteins With Human Arterial Wall Proteoglycans

V. Anber; J. S. Millar; M. McConnell; J. Shepherd; ; C. J. Packard

From the University Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow G4 OSF, UK.

Correspondence to Dr Vian Anber, Department of Pathological Biochemistry, Glasgow Royal Infirmary, Alexandra Parade, Glasgow G4 OSF, UK.

Abstract The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, S_f 60 to 400; VLDL2, S_f 20 to 60; IDL1, S_f 16 to 20; IDL2, S_f 12 to 16; LDLA, S_f 8 to 12; and LDLB, S_f 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL S_f 12 to 16 LDL S_f 8 to 12 > LDL S_f 0 to 8 > IDL S_f 16 to 20 >> VLDL S_f 20 to 60 > VLDL S_f 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm, of APG with IDL S_f 12 to 16 and LDL S_f 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of S_f 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease.

Key Words: atherogenic lipoprotein phenotype • LDL subfractions • sialic acid • ciprofibrate

This article has been cited by other articles:

				I. H. de Boer, B. C. Astor, H. Kramer, W. Palmas, S. L. Seliger, M. G. Shlipak, D. S. Siscovick, M. Y. Tsai, and B. Kestenbaum Lipoprotein Abnormalities Associated with Mild Impairment of Kidney Function in the Multi-Ethnic Study of Atherosclerosis Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 125 - 132. [Abstract] [Full Text] [PDF]

				I. Gazi, E. S. Lourida, T. Filippatos, V. Tsimihodimos, M. Elisaf, and A. D. Tselepis Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Small, Dense LDL Particles in Human Plasma Clin. Chem., December 1, 2005; 51(12): 2264 - 2273. [Abstract] [Full Text] [PDF]

				P. Davidsson, J. Hulthe, B. Fagerberg, B.-M. Olsson, C. Hallberg, B. Dahllof, and G. Camejo A proteomic study of the apolipoproteins in LDL subclasses in patients with the metabolic syndrome and type 2 diabetes J. Lipid Res., September 1, 2005; 46(9): 1999 - 2006. [Abstract] [Full Text] [PDF]

				S. Stan, E. Levy, E. E. Delvin, J. A. Hanley, B. Lamarche, J. O'Loughlin, G. Paradis, and M. Lambert Distribution of LDL Particle Size in a Population-Based Sample of Children and Adolescents and Relationship with Other Cardiovascular Risk Factors Clin. Chem., July 1, 2005; 51(7): 1192 - 1200. [Abstract] [Full Text] [PDF]

				Y. Bosse, L. Perusse, and M.-C. Vohl Genetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations J. Lipid Res., June 1, 2004; 45(6): 1008 - 1026. [Abstract] [Full Text] [PDF]

				A. Charest, S. Desroches, C. A. Vanstone, P. J. H. Jones, and B. Lamarche Unesterified Plant Sterols and Stanols Do Not Affect LDL Electrophoretic Characteristics in Hypercholesterolemic Subjects J. Nutr., March 1, 2004; 134(3): 592 - 595. [Abstract] [Full Text] [PDF]

				J. M. Lawrence, J. Reid, G. J. Taylor, C. Stirling, and J. P.D. Reckless Favorable Effects of Pioglitazone and Metformin Compared With Gliclazide on Lipoprotein Subfractions in Overweight Patients With Early Type 2 Diabetes Diabetes Care, January 1, 2004; 27(1): 41 - 46. [Abstract] [Full Text] [PDF]

				S. D. Proctor and J. C.L. Mamo Intimal Retention of Cholesterol Derived From Apolipoprotein B100- and Apolipoprotein B48-Containing Lipoproteins in Carotid Arteries of Watanabe Heritable Hyperlipidemic Rabbits Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1595 - 1600. [Abstract] [Full Text] [PDF]

				G. Siegel, C. Abletshauser, M. Malmsten, A. Schmidt, and K. Winkler Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a receptor-based biosensor model Cardiovasc Res, June 1, 2003; 58(3): 696 - 705. [Abstract] [Full Text] [PDF]

				F. Pont, L. Duvillard, E. Florentin, P. Gambert, and B. Verges Early Kinetic Abnormalities of ApoB-Containing Lipoproteins in Insulin-Resistant Women With Abdominal Obesity Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1726 - 1732. [Abstract] [Full Text] [PDF]

				J. Vakkilainen, M. Jauhiainen, K. Ylitalo, I. O. Nuotio, J. S. A. Viikari, C. Ehnholm, and M.-R. Taskinen LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins J. Lipid Res., April 1, 2002; 43(4): 598 - 603. [Abstract] [Full Text] [PDF]

				R. M. Krauss Atherogenic Lipoprotein Phenotype and Diet-Gene Interactions J. Nutr., February 1, 2001; 131(2): 340S - 343. [Abstract] [Full Text]

				A. Pedersen, M. W. Baumstark, P. Marckmann, H. Gylling, and B. Sandström An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets J. Lipid Res., December 1, 2000; 41(12): 1901 - 1911. [Abstract] [Full Text]

				K. Öörni, M. O. Pentikäinen, M. Ala-Korpela, and P. T. Kovanen Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions J. Lipid Res., November 1, 2000; 41(11): 1703 - 1714. [Abstract] [Full Text]

				S. Lepage, F. Nigon, D. Bonnefont-Rousselot, U. Assogba, S. Goulinet, L. Chancharme, J. Delattre, E. Bruckert, and M. J. Chapman Oxidizability of Atherogenic Low-Density Lipoprotein Subspecies in Severe Familial Hypercholesterolemia: Impact of Long-Term Low-Density Lipoprotein Apheresis Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(2): 87 - 103. [Abstract] [PDF]

				C. Skoglund-Andersson, R. Tang, M. G. Bond, U. de Faire, A. Hamsten, and F. Karpe LDL Particle Size Distribution Is Associated With Carotid Intima-Media Thickness in Healthy 50-Year-Old Men Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2422 - 2430. [Abstract] [Full Text] [PDF]

				P. Sartipy, G. Camejo, L. Svensson, and E. Hurt-Camejo Phospholipase A2 Modification of Low Density Lipoproteins Forms Small High Density Particles with Increased Affinity for Proteoglycans and Glycosaminoglycans J. Biol. Chem., September 3, 1999; 274(36): 25913 - 25920. [Abstract] [Full Text] [PDF]

				L. Chancharme, P. Therond, F. Nigon, S. Lepage, M. Couturier, and M. J. Chapman Cholesteryl Ester Hydroperoxide Lability Is a Key Feature of the Oxidative Susceptibility of Small, Dense LDL Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 810 - 820. [Abstract] [Full Text] [PDF]

				N. F. Galeano, M. Al-Haideri, F. Keyserman, S. C. Rumsey, and R. J. Deckelbaum Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity J. Lipid Res., June 1, 1998; 39(6): 1263 - 1273. [Abstract] [Full Text]