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Studies of glycosaminoglycan composition and biologic activity of Vessel®, a hypolipidemic agent

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      Abstract

      Heparin-like glycosaminoglycans (GAG) were isolated from commercial Vessel® and their biologic properties studied. Vessel was found to be a mixture of chondroitin sulfates, dermatan sulfate and heparin-like GAG. Chondroitin sulfates and dermatan sulfate in Vessel® were hydrolyzed by chondroitinase ABC and the residual Vessel® was fractionated on a Dowex-1 Cl column eluting with a stepwise-increasing concentration of NaCl (1.2–4.0 M). The major fractions eluted at 1.6 M and 1.8 M NaCl were tentatively identified by chemical analysis as heparin-like GAG with somewhat lower sulfate content than standard heparin. Both fractions had lipoprotein lipase-releasing activity and anticoagulant activity similar to heparin, but 1.6 M NaCl fraction had a third of the anticoagulant activity of standard heparin. The 1.8 M NaCl fraction complexed with serum lipoproteins similarly to heparin. In preliminary studies cholesterol-fed rabbits treated with Vessel® exhibited somewhat less atherosclerosis than controls.

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      References

        • Constantinides P.
        • Szasz G.
        • Harder F.
        Retardation of atheromatosis and adrenal enlargement by heparin in the rabbit.
        Arch. Path. 1953; 56: 36
        • Horlick L.
        • Duff G.L.
        Heparin in experimental cholesterol atherosclerosis in the rabbit, Part 1 (Effect of heparin on the serum lipids and the development of atherosclerosis).
        Arch. Path. 1954; 57: 417
        • Meng H.C.
        • Davis W.S.
        Effects of heparin on development of atherosclerosis and fatty liver.
        Arch. Path. 1955; 60: 276
        • Rowsell H.C.
        • Murphy E.A.
        • Mustard J.F.
        Heparin dosage and atherogenesis in the rabbit.
        Arch. Path. 1965; 80: 63
        • Engelberg H.
        • Kuhn R.
        • Steinman M.
        Controlled study of the effect of intermittent heparin therapy on the course of human coronary atherosclerosis.
        Circulation. 1956; 13: 489
        • Bottiger L.E.
        • Carlson L.A.
        • Engstedt L.
        • Oro L.
        Effect of long-term heparin treatment in ischaemic heart disease.
        J. Atheroscler. Res. 1965; 5: 253
        • Bottiger L.E.
        • Carlson L.A.
        • Engstedt L.
        • Oro L.
        Long-term heparin treatment in ischaemic heart disease — Effects on clinical condition and plasma lipids.
        Acta Med. Scand. 1967; 182: 245
        • Morrison L.M.
        • Schjeide O.A.
        Coronary Heart Disease and the Mucopolysaccharides (Glycosaminoglycans).
        Charles C. Thomas, Springfield, IL1974.a
        • Bianchini P.
        • Osima B.
        • Casetta R.
        • Bramanti G.
        • Mostacci C.
        Un nuovo eparinoide pancreatico attivo sul metabolismo lipidico.
        Giornale Dell' Arteriosclerosi. 1967; 3: 327
        • Seethanathan P.
        • Dalferes Jr., E.R.
        • Radhalnishnamurthy B.
        • Victor R.
        • Berenson G.S.
        Glycosaminoglycans from Ateroid® and bovine duodenal mucosa and pancreas.
        Mol. Cell. Biochem. 1975; 8: 177
      1. Biavati, G., Personal communication.

        • Bitter T.
        • Muir H.M.
        A modified uronic acid carbazole reaction.
        Anal. Biochem. 1962; 4: 330
        • Boas N.F.
        Method for determination of hexosamines in tissues.
        J. Biol. Chem. 1953; 204: 553
        • Dodgson K.
        • Spencer B.
        Studies on sulfatases, Part 5 (The determination of inorganic sulfate in the study of sulfates).
        Biochem. J. 1953; 55: 436
        • Muir H.
        The nature of the link between protein and carbohydrate of chondroitin sulfate complex from hyaline cartilage.
        Biochem. J. 1958; 69: 195
        • Lagunoff D.
        • Warren G.
        Determination of 2-deoxy-2-sulfoamino hexose content of mucopolysaccharides.
        Arch. Biochem. Biophys. 1962; 99: 396
        • Radhakrlshnamurthy B.
        • Dalferes Jr., E.R.
        • Berenson G.S.
        Determination of hexosamines by gas-liquid chromatography.
        Anal. Biochem. 1966; 17: 545
        • Radhaluishnamurthy B.
        • Dalferes Jr., E.R.
        • Berenson G.S.
        Analysis of glycosaminoglycans by gas liquid chromatography and the nature of hexuronic acids in heparin.
        Anal. Biochem. 1968; 24: 397
        • Radhakrishnamurthy B.
        • Dalferes Jr., E.R.
        • Berenson G.S.
        Determination of N-acetyl groups in glycosaminoglycans by gas-liquid chromatography.
        Anal. Biochem. 1968; 26: 61
        • Srinivasan S.R.
        • Radhakrishnamurthy B.
        • Dalferes Jr., E.R.
        • Berenson G.S.
        Determination of sulfate in glycosaminoglycans by gas-liquid chromatography.
        Anal. Biochem. 1970; 35: 398
        • Matalon R.
        • Dorfman A.
        Hurler's syndrome — Biosynthesis of acid mucopolysaccharides in tissue culture.
        in: Proc. Nat. Acad. Sci. (U.S.A.). 56. 1966: 1310
        • Radhakrishnamurthy B.
        • Dalferes Jr., E.R.
        • Ruiz H.A.
        • Berenson G.S.
        Determination of aorta glycosaminoglycans by automated ion-exchange chromatography.
        Anal. Biochem. 1977; 82: 445
        • Schiller S.
        • Slover G.A.
        • Dorfman A.
        A method for the separation of acid mucopolysaccharides — Its application to the isolation of heparin from the skin of rats.
        J. Biol. Chem. 1961; 236: 983
        • Yamagata T.
        • Saito H.
        • Habuchi O.
        • Suzuki S.
        Purification and properties of bacterial chondroitinases and chondrosulfatases.
        J. Biol. Chem. 1968; 243: 1523
        • Jacques L.B.
        • Charles A.F.
        The assay of heparin.
        Quart. J. Pharm. 1941; 14: 415
        • Korn E.D.
        Lipoprotein lipase (clearing factor).
        in: Methods in Enzymology. Vol. 5. Academic Press, New York, NY1962: 542
        • Hanahan D.J.
        • Olley J.N.
        Chemical nature of monophosphoinositides.
        J. Biol. Chem. 1958; 231: 813
        • Srinivasan S.R.
        • Lopez-S A.
        • Radhakrishnamurthy B.
        • Berenson G.S.
        Complexing of serum pre-β- and β-ipoproteins and acid mucopolysaccharides.
        Atherosclerosis. 1970; 12: 321
        • Srinivasan S.R.
        • Lopez-S A.
        • Radhakrishnamurthy B.
        • Berenson G.S.
        A simplified technique for semiquantitative, clinical estimation of serum β- and pre-β-lipoproteins.
        Angiologica. 1970; 7: 344
        • Berenson G.S.
        • Srinivasan S.R.
        • Pargaonkar P.S.
        • Radhakrishnamurthy B.
        • Dalferes Jr., E.R.
        Clinical application of an indirect method for quantitating serum lipoproteins.
        Clin. Chim. Acta. 1972; 36: 175
        • Pearson S.
        • Sterns T.H.
        • McGavaek T.H.
        A rapid, accurate method for the determination of total cholesterol in serum.
        Anal. Chem. 1953; 25: 813
        • Guzman M.A.
        • McMahan C.A.
        • McGill Jr., H.C.
        • Strong J.P.
        • Tejada C.
        • Restrepo C.
        • Eggen D.A.
        • Robertson W.B.
        • Solberg L.A.
        Selected methodologic aspects of the international atherosclerosis project.
        Lab. Invest. 1968; 18: 479
        • Cifonelli J.A.
        Relation of chemical structure of heparin to its anticoagulant activity.
        in: Bradshaw R.A. Wessler S. Heparin — Structure, Function and Clinical Applications (Advances in Experimental Medicine and Biology). Plenum Press, New York, NY1974: 95
        • Dietrich C.P.
        Novel heparin degradation products.
        Biochem. J. 1968; 108: 647
        • 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
        • Srinivasan S.R.
        • Dolan P.
        • Radhakrishnamurthy B.
        • Berenson G.S.
        Lipoprotein-acid mucopolysaccharide complexes of human atherosclerotic lesions.
        Biochem. Biophys. Acta. 1975; 338: 58
        • Mawhinney T.P.
        • Augustyn J.M.
        • Fritz K.F.
        Isolation and characterization of glycosaminoglycans-lipoprotein complexes from aortas of hypercholesterolemic rabbits.
        in: Fed. Proc.34. 1975: 875
        • Grossman B.J.
        • Cifonelli J.A.
        • Ozoa A.K.
        Inhibition of atherosclerosis in cholesterol-fed rabbits by a heparitin sulfate.
        Atherosclerosis. 1971; 13: 103
        • Nakashima Y.
        • DiFerrante N.
        • Jackson R.L.
        • Pownall H.J.
        The interaction of human plasma glycosaminoglycans with plasma lipoproteins.
        J. Biol. Chem. 1975; 250: 5386
        • Zilversmit D.B.
        A proposal linking atherogenesis of the interaction of endothelial lipoprotein lipase with triglyceride-rich lipoproteins.
        Circ. Res. 1973; 33: 633
        • Olivecrona T.
        • Egelrud T.
        Evidence for an ionic binding of lipoprotein lipase to heparin.
        Biochem. Biophys. Res. Commun. 1971; 43: 524