Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.
The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent.
Pacheco
R G
RG
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ, Brazil.
Vicente
C P
CP
Zancan
P
P
Mourão
P A
PA
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004447:Echinodermata / Q000737:chemistry*; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D005643:Fucose / Q000737:chemistry; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D051381:Rats; D013462:Sulfur Radioisotopes; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D013462:Sulfur Radioisotopes; D003871:Dermatan Sulfate; D005643:Fucose; D006493:Heparin; D002809:Chondroitin Sulfates