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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44774

Holy, E W; Tanner, F C (2010). Tissue factor in cardiovascular disease pathophysiology and pharmacological intervention. Advances in Pharmacology, 59:259-292.

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Abstract

Tissue factor (TF) is the major trigger of the coagulation cascade and thereby crucially involved in the maintenance of vascular hemostasis. By binding factor VIIa, the resulting TF:VIIa complex activates the coagulation factors IX and X ultimately leading to fibrin and clot formation. In the vessel wall, TF expression and activity is detectable in vascular smooth muscle cells and fibroblasts and, at a much lower level, in endothelial cells and can be induced by various stimuli including cytokines. In addition, TF is found in the bloodstream in circulating cells such as monocytes, in TF containing microparticles, and as a soluble splicing isoform. Besides its well-known extracellular role as a trigger of coagulation, TF also functions as a transmembrane receptor, and TF-dependent intracellular signaling events regulate the expression of genes involved in cellular responses such as proliferation and migration. TF indeed appears to be involved in the pathogenesis of neointima formation and tumor growth, and increased levels of TF have been detected in patients with cardiovascular risk factors or coronary artery disease as well as in those with cancer. Therefore, pharmacological or genetic inhibition of TF may be an attractive target for the treatment of cardiovascular disease and cancer. Different strategies for inhibition of TF have been developed such as inhibition of TF synthesis and blockade of TF action. Clinical applications of such strategies need to be tested in appropriate trials, in particular for evaluating the advantages of targeted versus systemic delivery of the inhibitors.

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9 citations in Web of Science®
8 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:10 Feb 2011 15:49
Last Modified:18 Dec 2013 12:04
Publisher:Elsevier
ISSN:1054-3589
Publisher DOI:10.1016/S1054-3589(10)59009-4
PubMed ID:20933205

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