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Role of Thrombin and Plasminogen Activators, Essential Proteases of the Coagulation and Fibrinolysis Cascades, in Fibrin Homeostasis and Vascular Cell Activation

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Vascular Endothelium

Part of the book series: NATO ASI Series ((NSSA,volume 281))

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Abstract

Coagulation and fibrinolysis regulate the formation and removal of fibrin, the temporary repair matrix in wounded areas of the body. The fibrin matrix acts as a sealing meshwork enforcing the hemostatic plug and preventing further blood loss after wounding, and provides a scaffold into which new microvessels or other invading cells can grow during wound healing. The formation of the fibrin matrix is initiated by proteolytic conversion of fibrinogen to fibrin by thrombin, a serine protease formed by the coagulation pathway. The matrix is strengthened by crosslinking of the fibrin subunits in fibrin fibers by factor XIII. Thrombin, the eventual product of the activated coagulation system, not only initiates fibrin formation and platelet activation, but also acts as a paracrine hormone at the vessel wall. On the endothelium, it interacts with two receptors and thereby enhances anticoagulant properties of the endothelium. The first receptor, thrombomodulin, catalyzes thrombin-dependent activation of protein C; upon thrombin binding, the other receptor activates the endothelial cell, by which acute release of u-PA and production of prostacyclin and NO is induced, and the cell is activated to synthesize new proteins. Thrombin also acts on smooth muscle cells, in particular in the thickened intima, via the thrombin receptor, and may stimulate the growth of smooth muscle cells. Hence, thrombin initiates and regulates fibrin formation; and activates vascular cells.

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Authors and Affiliations

  1. Gaubius Laboratory TNO-PG, Leiden, The Netherlands

    Victor W. M. van Hinsbergh

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  1. Victor W. M. van Hinsbergh
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  1. Medical College of Georgia, Augusta, Georgia, USA

    John D. Catravas

  2. Boston University School of Medicine, Boston, Massachusetts, USA

    Allan D. Callow

  3. T Cell Sciences, Inc., Needham, Massachusetts, USA

    Una S. Ryan

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© 1996 Plenum Press, New York

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van Hinsbergh, V.W.M. (1996). Role of Thrombin and Plasminogen Activators, Essential Proteases of the Coagulation and Fibrinolysis Cascades, in Fibrin Homeostasis and Vascular Cell Activation. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0355-8_5

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  • DOI: https://doi.org/10.1007/978-1-4613-0355-8_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8013-9

  • Online ISBN: 978-1-4613-0355-8

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