Sato Y, Asada Y, Marutsuka K, Hatakeyama K, Kamikubo Y, Sumiyoshi A
First Department of Pathology, Miyazaki Medical College, Kiyotake, Japan.
Thromb Haemost. 1997 Sep;78(3):1138-41.
Tissue factor (TF), a transmembrane glycoprotein, forms a high affinity complex with factor VII/VIIa (FVIIa) and thereby initiates blood coagulation. Tissue factor pathway inhibitor (TFPI) is an endogenous protease inhibitor of TF/FVIIa-initiated coagulation. We previously reported that TF was a strong chemotactic factor for cultured vascular smooth muscle cells (SMCs). In this study, we examined the contribution of FVIIa and the effect of TFPI to TF-induced cultured SMC migration. TF/FVIIa complex showed a strong migration ability, however, neither TF alone nor FVIIa induced SMC migration. TF/FVIIa treated by a serine protease inhibitor and the complex of TF and inactivated FVIIa (DEGR-FVIIa) did not stimulate SMC migration. Pretreatment with hirudin and the antibodies to alpha-thrombin and factor X had no effect on TF/FVIIa-induced SMC migration, although alpha-thrombin and factor Xa also induced SMC migration respectively. TFPI markedly inhibited TF/FVIIa-induced SMC migration in a concentration-dependent manner, but did not affect the SMC migration induced by platelet-derived growth factor (PDGF)-BB, basic fibroblast-growth factor (bFGF), or alpha-thrombin. These results indicate that the catalytic activity of TF/FVIIa complex is important on SMC migration, and TFPI can reduce SMC migration as well as thrombosis.
组织因子（TF）是一种跨膜糖蛋白，它与因子VII/VIIa（FVIIa）形成高亲和力复合物，从而启动血液凝固。组织因子途径抑制剂（TFPI）是TF/FVIIa启动的凝血过程中的一种内源性蛋白酶抑制剂。我们之前报道过TF是培养的血管平滑肌细胞（SMC）的一种强趋化因子。在本研究中，我们研究了FVIIa的作用以及TFPI对TF诱导的培养SMC迁移的影响。TF/FVIIa复合物显示出很强的迁移能力，然而，单独的TF或FVIIa均未诱导SMC迁移。用丝氨酸蛋白酶抑制剂处理的TF/FVIIa以及TF与失活的FVIIa（DEGR-FVIIa）的复合物均未刺激SMC迁移。尽管α-凝血酶和因子Xa也分别诱导SMC迁移，但用水蛭素以及针对α-凝血酶和因子X的抗体进行预处理对TF/FVIIa诱导的SMC迁移没有影响。TFPI以浓度依赖性方式显著抑制TF/FVIIa诱导的SMC迁移，但不影响血小板衍生生长因子（PDGF）-BB、碱性成纤维细胞生长因子（bFGF）或α-凝血酶诱导的SMC迁移。这些结果表明，TF/FVIIa复合物的催化活性对SMC迁移很重要，并且TFPI可以减少SMC迁移以及血栓形成。
