doi: 10.1161/01.RES.0000172745.09928.87
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© 2005 American Heart Association, Inc.
Editorials |
Soluble Tissue Factor Emerges From Inflammation
From the Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany.
Correspondence to I. Ott, Deutsches Herzzentrum, Lazarettstr. 36, 80636 München, Germany. E-mail ott@dhm.mhn.de
See related article, pages 1233–1239
Key Words: coagulation • inflammation
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Inflammation and coagulation play crucial roles in the pathogenesis of vascular disease. Growing evidence reveals a tight mutual network in which inflammation not only activates coagulation, but coagulation also feeds back to inflammatory activity. Tissue factor (TF), as the cellular initiator of the extrinsic coagulation pathway, plays a key role in this cross-talk. The activation of coagulation and the deposition of fibrin are well characterized consequences of inflammation and can be viewed as an essential part of the host defense reaction. Under certain conditions, however, coagulation may contribute to excessive thrombus formation, and the recruitment of inflammatory cells to a ruptured atherosclerotic plaque may provoke subsequent myocardial infarction. Expression of TF by inflammatory cells in the unstable plaque can initiate the extrinsic coagulation cascade, and the thrombin thus generated can activate platelets and lead to the formation of a platelet–fibrin thrombus. Systemic inflammatory changes that occur in severe sepsis also induce TF expression in monocytes and increase the number of circulating procoagulant microparticles.1,2 The subsequent intravascular coagulation may contribute to multiple organ dysfunctions. In addition, coagulation can markedly increase the inflammatory cell activity and, thereby, aggravate organ damage even further. Coagulation factors activate protease-activated receptors (PARs) on mononuclear or endothelial cells and thereby contribute to cytokine generation or inflammatory cell apoptosis.2,3 Elegant experiments in genetically modified mice identified the key role of TF and PARs in coagulation-induced inflammation during endotoxemia. A decrease in TF activity in low TF or a PAR-2 deficiency in combination with thrombin inhibition abrogated systemic inflammatory
Related Article:
Circ. Res. 2005 96: 1233-1239.