Tissue factor pathway inhibitor: a possible mechanism of action.
We have analyzed several mathematical models that describe inhibition of the factor VIIa-tissue factor complex (VIIa-TF) by tissue factor pathway inhibitor (TFPI). At the core of these models is a common mechanism of TFPI action suggesting that only the Xa-TFPI complex is the inhibitor of the extrinsic tenase activity. However, the model based on this hypothesis could not explain well all the available experimental data. Here, we show that a good quantitative description of all experimental data could be achieved in a model that contains two more assumptions. The first assumption is based on the hypothesis originally proposed by Baugh et al. [Baugh, R.J., Broze, G.J. Jr & Krishnaswamy, S. (1998) J. Biol. Chem. 273, 4378-4386], which suggests that TFPI could inhibit the enzyme-product complex Xa-VIIa-TF. The second assumption proposes an interaction between the X-VIIa-TF complex and the factor Xa-TFPI complex. Experiments to test these hypotheses are suggested.
Panteleev
Mikhail A
MA
National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia.
Zarnitsina
Veronica I
VI
Ataullakhanov
Fazoil I
FI
D001777:Blood Coagulation / Q000502:physiology; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005170:Factor X / Q000819:agonists* / Q000378:metabolism; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D046911:Macromolecular Substances; D008954:Models, Biological; D011485:Protein Binding; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008074:Lipoproteins; D046911:Macromolecular Substances; C051928:lipoprotein-associated coagulation inhibitor; D005170:Factor X; D013925:Thromboplastin; D015942:Factor VIIa