Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility

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      An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta-derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight > 5.0 × 106 daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per μG PG was demonstrated (r = 0.87, P < 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 × 106 and 4.8 × 106 daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant (r = 0.67, P < 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size.


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        • Smith E.B.
        The influence of age and atherosclerosis on the chemistry of aortic intima. Part 2. Collagen and mucopolysaccharides.
        J. Atheroscler. Res. 1965; 5: 241
        • Srinivasan S.R.
        • Dolan P.
        • Radhakrishnamurthy B.
        • Berenson G.S.
        Isolation of lipoprotein-acid mucopolysaccharide complexes from fatty streaks of human aortas.
        Atherosclerosis. 1972; 16: 95
        • Adams C.W.M.
        • Bayliss O.B.
        Acid mucosubstances underlying lipid deposits in aging tendons and atherosclerotic arteries.
        Atherosclerosis. 1973; 18: 191
        • Mawhinney T.P.
        • Augustyn J.M.
        • Fritz K.E.
        Glycosaminoglycan-lipoprotein complexes from aortas of hypercholesterolemic rabbits. Part I. Isolation and characterization.
        Atherosclerosis. 1978; 31: 155
        • Camejo G.
        • Lalaguna F.
        • Lopez F.
        • Starosta R.
        Characterization and properties of a lipoprotein-complexing proteoglycan from human aorta.
        Atherosclerosis. 1980; 35: 307
        • Mourao P.A.S.
        • Bracamonte C.A.
        The binding of human aortic glycosaminoglycans and proteoglycans to plasma low density lipoproteins.
        Atherosclerosis. 1984; 50: 133
        • Avila E.M.
        • Lopez F.
        • Camejo G.
        Properties of low density lipoprotein related to its interaction with arterial wall components: in vitro and in vivo studies.
        Artery. 1978; 4: 36
        • Steele R.H.
        • Wagner W.D.
        • Rowe H.A.
        • Edwards I.J.
        Artery wall derived proteoglycan-plasma lipoprotein interaction: lipoprotein binding properties of extracted proteoglycans.
        Atherosclerosis. 1987; 65: 51
        • Steele R.H.
        • Wagner W.D.
        Lipoprotein interaction with artery wall derived proteoglycan: comparisons between atherosclerosis-susceptible WC-2 and resistant Show Racer pigeons.
        Atherosclerosis. 1987; 65: 63
        • Barakat H.A.
        • St.Clair R.W.
        Characterization of plasma lipoproteins of grain- and cholesterol-fed White Carneau and Show Racer pigeons.
        J. Lipid Res. 1985; 26: 1252
        • Rudel L.L.
        • Leathers C.W.
        • Bond M.G.
        • Bullock B.C.
        Dietary ethanol-induced modifications in hyperlipoproteinemia and atherosclerosis in nonhuman primates (Macaca nemestrina).
        Arteriosclerosis. 1981; 1: 144
        • Rush R.L.
        • Leon L.
        • Turrell J.
        Automated cholesterol and triglyceride determination of the AutoAnalyzer II.
        in: Barton E.C. Advances in Automated Analysis. 7th edn. Technicon International Congress, 1970. Vol. I. Futura Publishing Company, New York1971: 503
        • Rudel L.L.
        • Pitts II, L.L.
        • Nelson C.A.
        Characterization of plasma low density lipoproteins of nonhuman primates fed dietary cholesterol.
        J. Lipid Res. 1977; 18: 211
        • St. Clair R.W.
        • Randolph R.K.
        • Jokinen M.P.
        • Clarkson T.B.
        • Barakat H.A.
        Relationship of plasma lipoproteins and the monocyte-macrophage system to atherosclerosis severity in cholesterol-fed pigeons.
        Arteriosclerosis. 1986; 6: 614
        • Wight T.N.
        • Hascall V.C.
        Proteoglycans in primate arteries. III. Characterization of the proteoglycans synthesized by arterial smooth muscle cells in culture.
        J. Cell Biol. 1983; 96: 167
        • Wagner W.D.
        • Clarkson T.B.
        • Feldner M.A.
        • Prichard R.W.
        The development of pigeon strains with selected atherosclerosis characteristics.
        Exp. Mol. Pathol. 1973; 19: 304
        • Camejo G.
        • Waich S.
        • Mateu L.
        • Acquatella H.
        • Lalaguna F.
        • Quintero G.
        • Berrizbeitia M.L.
        Differences in the structure of plasma low density lipoproteins and their relationship to the extent of interaction with arterial wall components.
        Ann. N.Y. Acad. Sci. 1976; 275: 153
        • Camejo G.
        • Mateu L.
        • Lalaguna F.
        • Padron R.
        • Waich S.
        • Acquatella H.
        • Vega H.
        Structural individuality of human serum LDL associated with a differential affinity for a macromolecular component of the arterial wall.
        Artery. 1976; 2: 79
        • Camejo G.
        • Lopez A.
        • Lopez F.
        • Quinons J.
        Interaction of low density lipoproteins with arterial proteoglycans. The role of charge and sialic acid content.
        Atherosclerosis. 1985; 55: 93
        • Iverius P-H.
        The interaction between human plasma lipoproteins and connective tissue glycosaminoglycans.
        J. Biol. Chem. 1972; 247: 2607
        • St.Clair R.W.
        • Mitschelen J.J.
        • Leight M.A.
        Metabolism by cells in culture of low density lipoproteins of abnormal composition from nonhuman primates with diet induced hypercholesterolemia.
        Biochim. Biophys. Acta. 1980; 618: 63
        • St. Clair R.W.
        • Greenspan P.
        • Leight M.A.
        Enhanced cholesterol delivery to cells in culture by low density lipoproteins from hypercholesterolemic monkeys.
        Arteriosclerosis. 1983; 3: 77
        • Hoff H.F.
        • Bradley W.A.
        • Heideman C.L.
        • Gaubatz J.W.
        • Karagas M.D.
        • Gotto Jr., A.M.
        Characterization of low density lipoprotein like particles in the human aorta from grossly normal and atherosclerotic regions.
        Biochem. Biophys. Acta. 1979; 573: 361
        • Hollander W.
        • Paddock J.
        • Colombo M.
        Lipoproteins in human atherosclerotic vessels. I. Biochemical properties of arterial low density lipoproteins, very low density lipoproteins and high density lipoproteins..
        Exp. Mol. Pathol. 1979; 30: 144
        • Goldstein J.L.
        • Hoff H.F.
        • Ho Y.K.
        • Basu S.K.
        • Brown M.S.
        Stimulation of cholesteryl ester synthesis in macrophages by extracts of atherosclerotic human aortas and complexes of albumin/cholesteryl esters.
        Arteriosclerosis. 1981; 3: 210
        • Salisbury B.G.J.
        • Falcone D.J.
        • Minick C.R.
        Insoluble low-density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages.
        Am. J. Pathol. 1985; 120: 6
        • Vijayagopal P.
        • Srinivasan S.R.
        • Jones K.M.
        • Radhakrishnamurthy B.
        • Berenson G.S.
        Complexes of lowdensity lipoproteins and proteoglycan aggregates promote cholesteryl ester accumulation in mouse macrophages.
        Biochim. Biophys. Acta. 1985; 837: 251
        • Rowe H.A.
        • Wagner W.D.
        Arterial dermatan sulfate proteoglycan structure in pigeons susceptible to atherosclerosis.
        Arteriosclerosis. 1985; 5: 101