This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Steffel, J. Articles by Tanner, F. C. Search for Related Content PubMed PubMed Citation Articles by Steffel, J. Articles by Tanner, F. C. Pubmed/NCBI databases Substance via MeSH Related Collections Pathophysiology Arterial thrombosis Coagulation Other Treatment Acute coronary syndromes

(Circulation. 2006;113:722-731.)
© 2006 American Heart Association, Inc.

Basic Science for Clinicians

Tissue Factor in Cardiovascular Diseases

Molecular Mechanisms and Clinical Implications

Jan Steffel, MD; Thomas F. Lüscher, MD; Felix C. Tanner, MD

From Cardiovascular Research, Physiology Institute, University of Zürich, Center for Integrative Human Physiology, University of Zürich, and Cardiology, Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland.

Correspondence to Felix C. Tanner, MD, Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. E-mail felix.tanner{at}access.unizh.ch

Tissue factor (TF), formerly known as thromboplastin, is the key initiator of the coagulation cascade; it binds factor VIIa resulting in activation of factor IX and factor X, ultimately leading to fibrin formation. TF expression and activity can be induced in endothelial cells, vascular smooth muscle cells, and monocytes by various stimuli such as cytokines, growth factors, and biogenic amines. These mediators act through diverse signal transduction mechanisms including MAP kinases, PI3-kinase, and protein kinase C. Cellular TF is present in three pools as surface, encrypted, and intracellular protein. TF can also be detected in the bloodstream, referred to as circulating or blood-borne TF. Elevated levels of TF are observed in patients with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking as well as in those with acute coronary syndromes. TF may indeed be involved in the pathogenesis of atherosclerosis by promoting thrombus formation; in addition, it can induce migration and proliferation of vascular smooth muscle cells. As a consequence, therapeutic strategies have been developed to specifically interfere with the action of TF such as antibodies against TF, site-inactivated factor VIIa, or recombinant TF pathway inhibitor. Inhibition of TF action appears to be an attractive target for the treatment of cardiovascular diseases.

Key Words: atherosclerosis • coagulation • myocardial infarction • thrombosis

This article has been cited by other articles:

				M. A. Sardo, S. Campo, G. Mandraffino, C. Saitta, A. Bonaiuto, M. Castaldo, M. Cinquegrani, G. Pizzimenti, and A. Saitta Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness Clin. Chem., May 1, 2008; 54(5): 814 - 823. [Abstract] [Full Text] [PDF]

				S.K. Payeli, R. Latini, C. Gebhard, A. Patrignani, U. Wagner, T.F. Luscher, and F.C. Tanner Prothrombotic Gene Expression Profile in Vascular Smooth Muscle Cells of Human Saphenous Vein, but Not Internal Mammary Artery Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 705 - 710. [Abstract] [Full Text] [PDF]

				B. E. Stahli, A. Breitenstein, A. Akhmedov, G. G. Camici, K. Shojaati, N. Bogdanov, J. Steffel, D. Ringli, T. F. Luscher, and F. C. Tanner Cardiac Glycosides Regulate Endothelial Tissue Factor Expression in Culture Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2769 - 2776. [Abstract] [Full Text] [PDF]

				M. Y.K. Lee, H.-F. Tse, C.-W. Siu, S.-G. Zhu, R. Y.K. Man, and P. M. Vanhoutte Genomic Changes in Regenerated Porcine Coronary Arterial Endothelial Cells Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2443 - 2449. [Abstract] [Full Text] [PDF]

				J. Wang, S. A. Mahmud, P. B. Bitterman, Y. Huo, and A. Slungaard Histone Deacetylase Inhibitors Suppress TF-{kappa}B-dependent Agonist-driven Tissue Factor Expression in Endothelial Cells and Monocytes J. Biol. Chem., September 28, 2007; 282(39): 28408 - 28418. [Abstract] [Full Text] [PDF]

				M. Ghosh, H. Wang, Y. Ai, E. Romeo, J. P. Luyendyk, J. M. Peters, N. Mackman, S. K. Dey, and T. Hla COX-2 suppresses tissue factor expression via endocannabinoid-directed PPAR{delta} activation J. Exp. Med., September 3, 2007; 204(9): 2053 - 2061. [Abstract] [Full Text] [PDF]

				R. A. Shirk and G. P. Vlasuk Inhibitors of Factor VIIa/Tissue Factor Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1895 - 1900. [Abstract] [Full Text] [PDF]

				R. A. Bundey Endothelial cell mechanosensitivity. Focus on "Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types" Am J Physiol Cell Physiol, July 1, 2007; 293(1): C33 - C34. [Full Text] [PDF]

				Y. Zhao, S. Zhou, and C.-K. Heng Impact of Serum Amyloid A on Tissue Factor and Tissue Factor Pathway Inhibitor Expression and Activity in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1645 - 1650. [Abstract] [Full Text] [PDF]

				A. V. Finn, G. Nakazawa, M. Joner, F. D. Kolodgie, E. K. Mont, H. K. Gold, and R. Virmani Vascular Responses to Drug Eluting Stents: Importance of Delayed Healing Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1500 - 1510. [Abstract] [Full Text] [PDF]

				R. P. Giugliano, S. D. Wiviott, P. H. Stone, D. I. Simon, M. J. Schweiger, A. Bouchard, M. A. Leesar, M. A. Goulder, S. R. Deitcher, C. H. McCabe, et al. Recombinant Nematode Anticoagulant Protein c2 in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: The ANTHEM-TIMI-32 Trial J. Am. Coll. Cardiol., June 26, 2007; 49(25): 2398 - 2407. [Abstract] [Full Text] [PDF]

				T. F. Luscher, J. Steffel, F. R. Eberli, M. Joner, G. Nakazawa, F. C. Tanner, and R. Virmani Drug-Eluting Stent and Coronary Thrombosis: Biological Mechanisms and Clinical Implications Circulation, February 27, 2007; 115(8): 1051 - 1058. [Abstract] [Full Text] [PDF]

				T J Coats, E Brazil, M Heron, and P K MacCallum Impairment of coagulation by commonly used resuscitation fluids in human volunteers. Emerg. Med. J., November 1, 2006; 23(11): 846 - 849. [Abstract] [Full Text] [PDF]

				G. G. Camici, J. Steffel, A. Akhmedov, N. Schafer, J. Baldinger, U. Schulz, K. Shojaati, C. M. Matter, Z. Yang, T. F. Luscher, et al. Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation: A Potential Treatment Strategy for Drug-Eluting Stents Circulation, October 3, 2006; 114(14): 1512 - 1521. [Abstract] [Full Text] [PDF]