Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor/factor VIIa complex.
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.
Sato
Y
Y
First Department of Pathology, Miyazaki Medical College, Kiyotake, Japan.
Asada
Y
Y
Marutsuka
K
K
Hatakeyama
K
K
Kamikubo
Y
Y
Sumiyoshi
A
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015942:Factor VIIa / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D046911:Macromolecular Substances; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*
D005343:Fibrinolytic Agents; D008074:Lipoproteins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D015942:Factor VIIa