Different antithrombotic mechanisms among glycosaminoglycans revealed witha 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 th rombosis in a dose-dependent manner. We also compared the antithrombotic ac tion of the sea cucumber chondroitin sulfate with that of standard mammalia n glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular in jection of fucosylated chondroitin sulfate at the dose totally preventing t hrombus formation produced a much more intense modification of the plasma a nticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is po ssible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on m odifications of the plasma anticoagulant activity, but it may involve addit ional effects in the case of mammalian glycosaminoglycans, perhaps modifica tions induced in the cells of the vessel wall. The anticoagulant and possib ly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced w ith the decrease of the chain size of the polymer. Overall, the sulfated po lysaccharide from the invertebrate revealed an unequivocal effect in preven ting experimental venous thrombosis, is a useful tool to investigate the an tithrombotic action in mammals and may offer an alternative for future deve lopment of a new therapeutic agent. Blood Coagul Fibrinolysis 11:563-573 (C ) 2000 Lippincott Williams & Wilkins.