Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Hematology, Peripheral Vascular Disease, Cardiovascular System & Cardiology, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

The anti-coagulant effect of sulfated α-L-fucans (fucoidans) from brown algae (Phaeophyta) or marine invertebrates is well-documented. Like heparin, they abolish serine protease activity and in particular thrombin and factor Xa. However, only a few reports exist about the fucoidans’ anti-thrombotic activity. Some fucoidan inhibit microvascular thrombus formation in vivo and in the case of fucosylated chondroitin sulfate the antithrombotic effect could even be dissociated from the anti-coagulant activity. The exact mechanism, however, remains unknown. We therefore studied the antithrombotic effect of the recently isolated sulfated 1->3 α-L-fucan from Lessonia vadosa (Phaeophyta) under more physiological conditions. Polyanionic compounds can hamper von Willebrand factor (VWF) binding to its platelet receptor glycoprotein Ib (GPIb). Indeed, this fucoidan strongly inhibited the ristocetin induced VWF-GPIbα binding with an IC50 of 0.5nM (0.16µg/mL) in a VWF:RCo ELISA. The fucoidan further strongly reduced ristocetin induced aggregation of GPIbαβ/IX expressing CHO cells (CHO GPIbα/β/IX). In addition, 200nM of the fucoidan could completely abolish human platelet adhesion to collagen at arterial shear stress conditions in flow experiments with whole blood. At this concentration, it also inhibited the binding of washed platelets to ultra-large VWF multimers anchored to the surface of endothelial cells in perfusion experiments. In conclusion, we here show that the fucoidan of Lessonia vadosa is a strong inhibitor of the VWF-GPIbα interaction under physiological conditions. For this fucoidan, the anti-coagulant could not be dissociated from the antithrombotic effect. In order to fully characterize a potential antithrombotic, we will next assess whether fucosylated chondroitin sulfate also inhibits the VWF-GPIbα interaction and to which extent this contributes to the antithrombotic effect in vivo.