Giraux J L, Tapon-Bretaudière J, Matou S, Fischer A M
Laboratoire d'Hématologie, Hôpital Necker-Enfants Malades, Université Paris V, France.
Thromb Haemost. 1998 Oct;80(4):692-5.
Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has antithrombotic properties, the mechanism of which is not yet completely understood. Tissue factor pathway inhibitor (TFPI), which regulates the tissue factor-dependent pathway of blood coagulation, is released from the endothelium by heparin, a mechanism contributing to its antithrombotic activity. In this study, we demonstrated that fucoidan, as heparin, induces TFPI release from cultured human umbilical vein endothelial cells (HUVEC). The TFPI accumulation in the HUVEC supernatants depends on the incubation time and polysaccharide concentration. After 30 to 60 minutes of incubation, TFPI concentration (total antigen level) was twice higher in the presence of both polysaccharides than in their absence. After one hour of incubation, in the presence of increasing concentrations of each polysaccharide, an optimal stimulation was observed for 0.5 microg/ml of fucoidan and 5 microg/ml of heparin, as evidenced by a raise of the basal TFPI level: a 2-fold increase for the total antigen and a 3-fold increase for the free antigen. These data suggest that TFPI released from vascular endothelial cells may contribute to the antithrombotic effect of fucoidan.
岩藻聚糖硫酸酯是一种从褐藻中提取的硫酸化多糖，具有抗血栓形成特性，但其作用机制尚未完全明确。组织因子途径抑制物（TFPI）可调节凝血的组织因子依赖性途径，肝素可促使其从内皮细胞释放，这是肝素发挥抗血栓活性的作用机制之一。在本研究中，我们证实岩藻聚糖硫酸酯与肝素一样，可诱导培养的人脐静脉内皮细胞（HUVEC）释放TFPI。HUVEC上清液中TFPI的积累取决于孵育时间和多糖浓度。孵育30至60分钟后，两种多糖存在时的TFPI浓度（总抗原水平）比不存在时高出两倍。孵育一小时后，随着每种多糖浓度的增加，观察到0.5微克/毫升的岩藻聚糖硫酸酯和5微克/毫升的肝素具有最佳刺激效果，基础TFPI水平升高证明了这一点：总抗原增加2倍，游离抗原增加3倍。这些数据表明，血管内皮细胞释放的TFPI可能有助于岩藻聚糖硫酸酯的抗血栓作用。
