Panteleev Mikhail A, Zarnitsina Veronica I, Ataullakhanov Fazoil I
National Research Center for Hematology, Russian Academy of Medical Sciences, Moscow, Russia.
Eur J Biochem. 2002 Apr;269(8):2016-31. doi: 10.1046/j.1432-1033.2002.02818.x.
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.
我们分析了几种描述组织因子途径抑制剂（TFPI）对因子VIIa-组织因子复合物（VIIa-TF）抑制作用的数学模型。这些模型的核心是TFPI作用的一种常见机制，即只有Xa-TFPI复合物是外源性凝血酶原酶活性的抑制剂。然而，基于这一假设的模型并不能很好地解释所有现有的实验数据。在此，我们表明，在一个包含另外两个假设的模型中，可以对所有实验数据进行良好的定量描述。第一个假设基于Baugh等人最初提出的假设[Baugh, R.J., Broze, G.J. Jr & Krishnaswamy, S. (1998) J. Biol. Chem. 273, 4378-4386]，该假设表明TFPI可以抑制酶-产物复合物Xa-VIIa-TF。第二个假设提出了X-VIIa-TF复合物与因子Xa-TFPI复合物之间的相互作用。文中还提出了检验这些假设的实验。
