FIBRINOLYTIC AND ANTICOAGULANT ACTIVITIES OF HIGHLY SULFATED FUCOIDAN

A series of fucoidan [sulfated poly(L-fucopyranose)] derivatives were prepared by chemical sulfation and desulfation, and they were tested for their abilities to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation, clot lysis, and the inhibition of fibrin polymer formation. The magnitude of their activities was dependent upon the degree of sulfation. A striking feature of the sulfated fucoidan was that, unlike heparin, it stimulated t-PA-induced plasma clot lysis by protecting plasmin activity from alpha-2-plasmin inhibitor and decreased the rate of fibrin polymer formation. The inhibition of hyaluronic acid-mediated enhancement of fibrin clot formation was also observed with the fucoidan derivative. We also showed that highly sulfated fucoidan prevents significantly endotoxin-induced hepatic vein thrombosis in the hyperlipemic rat model. The present results are the first to describe the fibrinolytic and anticoagulant activities of fucoidan, and thus may provide useful clues for the development of an ideal thrombolytic agent.