TAILIEUCHUNG - Báo cáo Y học: 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 | Eur. J. Biochem. 269 2016-2031 2002 FEBS 2002 doi Tissue factor pathway inhibitor A possible mechanism of action Mikhail A. Panteleev Veronica I. Zarnitsina and Fazoil I. Ataullakhanov National Research Center for Hematology Russian Academy of Medical Sciences Moscow Russia 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 Iff 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 mdell bared on this hypothesis could not explain well all the available experimental data. Here we hl-iow dait a oood quantitative description of all experimental data could be achieved in a model that contains two more assumptions. The íĩitl assumption is based on the hypothesis originally proposed by Baugh et al. Baugh . Broze . Jr Krishna-swamy S. 11098 J. Biol. Chem. 273 4378 4386 which suggests that TFPI could inhibit the enzymeaproduct complex second assumption proposes an interaction between the XaVIIaaTF complex and the factor XaaTFPI complex. Experiments oo te t these hypotheses are suggested. Keywords blood coagulation extrinsic pathway tissue factor pathway inhibitor tissue factor mathematical model. Blood coagulation is initiated upon contact of the integral membrane glycoprotein tissue factor TF with plasma 1 2 . TF is present on membranes of tissue cells that are normally not in contact with blood. After vasutủr damgee TF ÍS exposed to plasma and binds to circulating factor VIIa greatly enhancing its proteolytic activity. The Wa-TF complex activates factors IX and X via limited proteolysis. This initiates a cascade of enzymatic reactions resulting ultimately in fibrin clot formation. The main requltna of the VIIa-TF complex activity is tissue factor pathway inhibitor TFPI 3 4 . FPPI irihiths Vna-FF .

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