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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activated factor V is a cofactor for the activation of factor XI by thrombin in plasma
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Activated factor V is a cofactor for the activation of factor XI by thrombin in plasma

机译：激活的因子V是血浆中凝血酶激活因子XI的辅助因子

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摘要

The mechanism by which the intrinsic pathway of coagulation contributes to physiological hemostasis is enigmatic. Thrombin activates factor XI, a key zymogen in this pathway, which leads to increased thrombin generation. As thrombin-dependent activation of factor XI in vitro is relatively inefficient, we hypothesized that a physiological cofactor supports this reaction in a plasma environment. We therefore investigated whether the cofactors of coagulation, activated factor V, activated factor VIII, high-molecular weight kininogen, or protein S, influenced activation of factor XI by thrombin. Only activated factor V stimulated activation of factor XI by thrombin in a purified system. Binding studies demonstrated that factor XI specifically interacts with both factor V and factor Va through multiple binding sites. We further investigated this cofactor function of activated factor V in plasma. Depletion of factor V, or the addition of activated protein C, decreased the activation of the intrinsic pathway by thrombin in plasma. However, activated protein C did not exert this effect in the plasma of a homo-zygous carrier of the prothrombotic factor V Leiden mutation. In conclusion, we propose a role for (activated) factor V as a cofactor in the activation of factor XI by thrombin. These findings offer insights into the coagulation system in both health and disease.
机译：内在的凝血途径促成生理止血的机制是未知的。凝血酶激活因子XI（该途径中的关键酶原），导致凝血酶生成增加。由于凝血酶依赖因子XI的体外激活效率相对较低，我们假设生理辅助因子在血浆环境中支持该反应。因此，我们研究了凝血因子，活化因子V，活化因子VIII，高分子量激肽原或蛋白质S的辅助因子是否影响凝血酶对因子XI的活化。在纯化的系统中，只有活化的因子V才能刺激凝血酶活化因子XI。结合研究表明，因子XI通过多个结合位点与因子V和因子Va特异性相互作用。我们进一步研究了血浆中活化因子V的这种辅助因子功能。因子V的耗竭或活化蛋白C的添加减少了血浆中凝血酶对内在途径的激活。但是，活化蛋白C在血栓前因子V Leiden突变的纯合子载体的血浆中没有发挥这种作用。总之，我们提出了（激活的）因子V作为凝血酶激活因子XI的辅助因子的作用。这些发现为健康和疾病中的凝血系统提供了见识。

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    Coen Maas; Joost C. M. Meijers; J. Arnoud Marquart; Kamran Bakhtiari; Cees Weeterings; Philip G. de Groot; Rolf T. Urbanus;

  • 作者单位

    Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;

    rnDepartment of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands;

    rnDepartment of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands;

    rnDepartment of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands;

    rnDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;

    rnDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;

    rnDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    coagulation; coagulation factor V; coagulation factor XI; feedback activation;

    机译：凝结;凝血因子V;凝血因子XI;反馈激活;

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