Unbalanced Effects of Dermatan Sulfates with Different Sulfation Patterns on Coagulation, Thrombosis and Bleeding

C. P. Vicente; P. Zancan; L. L. Peixoto; R. Alves-Sá; F. S. Araújo; P. A. S. Mourão; M. S. G. Pavão

doi:10.1055/s-0037-1616054

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 86(05): 1215-1220
DOI: 10.1055/s-0037-1616054

Review Article

Schattauer GmbH

Unbalanced Effects of Dermatan Sulfates with Different Sulfation Patterns on Coagulation, Thrombosis and Bleeding

C. P. Vicente

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

²Universidade do Grande Rio Professor José de Souza Herdy, Duque de Caxias, Rio de Janeiro, Brazil

,

P. Zancan

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

L. L. Peixoto

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

R. Alves-Sá

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

F. S. Araújo

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

P. A. S. Mourão

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

M. S. G. Pavão

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

› Institutsangaben

Abstract

Summary

We compared the anticoagulant, antithrombotic and bleeding effects of highly sulfated dermatan sulfates from invertebrates and their mammalian counterpart. An invertebrate dermatan sulfate containing 2-O-sulfated α-L-iduronic acid and 4-O-sulfated N-acetyl-β-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. It inhibits thrombin due to the formation of a covalent complex with heparin cofactor II, as in the case of mammalian dermatan sulfate, but the effect occurs at lower concentrations for the invertebrate polysaccharide. Surprisingly, the invertebrate dermatan sulfate has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, another invertebrate dermatan sulfate, also enriched in 2-O-sulfated α-L-iduronic acid, but in this case sulfated at O-6 position of the N-acetyl-β-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Overall, these results demonstrate unbalanced effects of dermatan sulfates with different sulfation patterns on coagulation, thrombosis and bleeding, and raise interesting questions concerning the relationship among these three biological actions of sulfated polysaccharides.

Keywords

Invertebrate dermatan sulfate - heparin cofactor II - anticoagulant - antithrombotic

Volltext

Referenzen

References
1 Kjellén L, Lindahl U. Proteoglycans: structures and interactions. Annu Rev Biochem 1991; 60: 443-75.
2 Scully MF, Ellis V, Seno N, Kakkar VV. Effect of oversulfated chondroitin and dermatan sulfate upon thrombin and factor Xa inactivation by antithrombin and heparin cofactor II. Biochem J 1988; 254: 547-51.
3 Maimone MM, Tollefsen DM. Structure of a dermatan sulfate hexasaccha-ride that binds to heparin cofactor II with high affinity. J Biol Chem 1990; 265: 18263-71.
4 Pavão MSG, Aiello KRM, Werneck CC, da Silva LCF, Valente AP, Mulloy B, Clowell NS, Tollefsen DM, Mourão PAS. Highly sulfated dermatan sulfates from ascidians: structure versus anticoagulant activity of these glycosaminoglycans. J Biol Chem 1998; 273: 27848-57.
5 Tollefsen DM, Majerus DW, Blank MK. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem 1982; 257: 2162-9.
6 Tollefsen DM, Pestka CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 1983; 258: 6713-6.
7 Agnelli G, Cosmi B, DiFilipo P, Ranucci V, Veschi F, Longetti M, Renga C, Barzi F, Gianese F, Lupattelli L, Rinonapoli E, Nenci GG. A randomised, doble-blind, placebo-controlled trial of dermatan sulfate for prevention of deep vein thrombosis in hip fracture. Thromb Haemost 1992; 67: 203-8.
8 Lane DA, Ryan K, Ireland H, Curtis JR, Nurmohamed MT, Roggekamp MC, Stevens P, Ten Cate JW. Dermatan sulfate in haemodialysis. Lancet 1992; 339: 334-5.
9 Barbanti M, Calanni F, Milani MR, Marchi E, Semeraro N, Colucci M. Therapeutic effect of a low molecular weight dermatan sulphate (Desmin 370) in rat vein thrombosis. Evidence for an anticoagulant-independent mechanism. Thromb Haemost 1993; 69: 147-51.
10 Barbanti M, Calanni F, Marchi E, Semeraro N, Colucci M. Desmin 370, a low molecular weight dermatan sulfate, reduces the weight of preformed thrombi in rats made afibrinogenemic by ancrod. Thromb Haemost 1995; 73: 287-90.
11 Abbadini M, Jin Zhu G, Maggi A, Pangrazzi J, Donati MB, Mussoni L. Dermatan sulfate induces plasminogen activator release in the perfused rat hindquarters. Blood 1987; 70: 1858-60.
12 Fernandez F, Buchanan MR, Hirsh J, Fenton JW, Ofusu F. Catalysis of thrombin inhibition provides an index for estimating the antithrombotic potential of glycosaminoglycans in rabbit. Thromb Haemost 1987; 57: 286-93.
13 Dol F, Caranobe C, Dupouy D, Petitou M, Lormeau JC, Choay J, Sié P, Boneau B. Effects of increased sulfation of dermatan sulfate on its in vitro and in vivo pharmacological properties. Thromb Res 1988; 52: 153-64.
14 Sie P, Dupouy D, Caranobe C, Petitou M, Boneu B. Antithrombotic properties of a dermatan sulfate hexadecasaccharide fractionated by affinity for heparin cofactor II. Blood 1993; 81: 1771-7.
15 Pavão MSG, Mourão PAS, Mulloy B, Tollefsen DM. A unique dermatan sulfate-like glycosaminoglycan from ascidian. Its structure and the effect of its unusual sulfation pattern on anticoagulant activity. J Biol Chem 1995; 270: 31027-36.
16 Scully MF, Ellis V, Seno N, Kakkar VV. Effect of oversulphated chondroitin and dermatan sulphate upon thrombin and factor Xa inactivation by antithrombin III or heparin cofactor II. Biochem J 1988; 254: 547-51.
17 Dietrich CP, Dietrich SMC. Electrophoretic behavior of acidic mucopolysaccharides in diamine buffers. Anal Biochem 1976; 70: 645-7.
18 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
19 Tollefsen DM, Blank MK. Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J Clin Invest 1981; 68: 589-96.
20 Fraker PJ, Speek Jr JC. Protein and cell membrane iodinations with a sparingly soluble chloramine, 1,3,4,6-tetrachloro-3α,6α-diphenylglycoluril. Biochem Biophys Res Commun 1978; 80: 849-57.
21 Farndale RW, Buttle DJ, Banet AJ. Improved quantitation and discrimination of sulfated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883: 173-7.
22 Wessler S, Reimer SM, Sheps MC. Biologic assay of a thrombosis inducing activity in human serum. J Appl Physiol 1959; 14: 943-6.
23 Anderson LO, Barrowcliffe TW, Holmer E, Johnson EA, Sims F. Anticoagulant properties of heparin fractionated by affinity chromatography on matrix-bound antithrombin-3 by gel filtration. Thromb Res 1976; 8: 859-67.
24 Herbert JM, Héralt JP, Bernat A, Van Amsterdan RGM, Vogel GMT, Lormeau JC, Petitou M, Meuleman DG. Biochemical and pharmacological properties of SANORG 32701. Comparison with the “synthetic pentasaccharide (SR 90107/org 31540)” and standard heparin. Circ Res 1996; 79: 590-600.
25 Parker KA, Tollefsen DM. The protease specificity of heparin cofactor II. Inhibition of thrombin generated during coagulation. J Biol Chem 1985; 260: 3501-5.
26 Griffith MJ, Noyes CM, Church FC. Reactive site peptide structural similarity between heparin cofactor II and antithrombin III. J Biol Chem 1985; 260: 2218-25.
27 Van Ryn-McKenna J, Ofusu FA, Hirsh J, Buchanan MR. Antithrombotic and bleeding effects of glycosaminoglycans different degress of sulphation. Br J Haematol 1989; 71: 265-9.
28 Hirsh J. Heparin induced bleeding. Nouv Rev Franç Hematol 1984; 26: 261-6.
29 Thomas DP, Roberts HR. Hypercoagulability in venous and arterial thrombosis. Ann Intern Med 1997; 126: 217-28.
30 Li JZ, Lian ECY. Aggregation of human platelets by acidic mucopolysaccharide extracted from Stichopus japonicus Selenka. Thromb Haemost 1988; 59: 435-9.