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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1653-1661. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-04-1148. This Article Full Text (PDF) All Versions of this Article: 2003-04-1148v1 103/5/1653    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kopp, C. W Articles by Minar, E. Search for Related Content PubMed PubMed Citation Articles by Kopp, C. W Articles by Minar, E. Social Bookmarking                   What's this? Submitted April 14, 2003 Accepted October 16, 2003 Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity Christoph W Kopp*, Thomas Hoelzenbein, Sabine Steiner, Rodrig Marculescu, Helga Bergmeister, Daniela Seidinger, Isabella Mosberger, Christoph Kaun, Manfred Cejna, Reinhard Horvat, Johann Wojta, Gerald Maurer, Bernd R Binder, Johannes M Breuss, Rupert C Ecker, Rainer de Martin, and Erich Minar Division of Angiology, University of Vienna Medical School, Vienna, Austria Division of Cardiology, University of Vienna Medical School, Vienna, Austria Department of Vascular Surgery, University of Vienna Medical School, Vienna, Austria Department of Biomedical Research, University of Vienna Medical School, Vienna, Austria Department of Angiography and Interventional Radiology, University of Vienna Medical School, Vienna, Austria Department of Pathology, University of Vienna Medical School, Vienna, Austria Department of Vascular Biology and Thrombosis Research, University of Vienna Medical School, Vienna, Austria Laboratory Medicine, University of Vienna Medical School, Vienna, Austria * Corresponding author; email: christoph.kopp{at}univie.ac.at. Activation of inflammatory and procoagulant mechanisms is thought to contribute significantly to the initiation of restenosis, a common complication after balloon angioplasty of obstructed arteries. During this process, expression of tissue factor (TF) represents one of the major physiologic triggers of coagulation that result in thrombus formation and the generation of additional signals leading to vascular smooth muscle cell (VSMC) proliferation and migration. In this study, we have investigated by which mechanisms inhibition of coagulation at an early stage through overexpression of tissue factor pathway inhibitor (TFPI), an endogenous inhibitor of TF, might reduce restenosis. In a rabbit femoral artery model, percutaneous delivery of TFPI using a recombinant adenoviral vector resulted in a significant reduction of the intima to media ratio 21 days after injury. When investigating several markers of inflammation and coagulation, we found reduced neointimal expression of monocyte chemoattractant protein-1, lesional monocyte infiltration, expression of vascular TF and matrix metalloproteinase-2 and -9. Moreover, overexpression of TFPI suppressed the autocrine release of PDGF-BB, MCP-1 and MMP-2 in response to factor VIIa and Xa from VSMC in vitro and inhibited monocyte TF-activity. These results suggest that TFPI exerts its action in vivo not only thorough thrombotic, but also non-thrombotic mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Stoll and M. Bendszus Inflammation and Atherosclerosis: Novel Insights Into Plaque Formation and Destabilization Stroke, July 1, 2006; 37(7): 1923 - 1932. [Abstract] [Full Text] [PDF] M. Wang, J. Zhang, G. Spinetti, L.-Q. Jiang, R. Monticone, D. Zhao, L. Cheng, M. Krawczyk, M. Talan, G. Pintus, et al. Angiotensin II Activates Matrix Metalloproteinase Type II and Mimics Age-Associated Carotid Arterial Remodeling in Young Rats Am. J. Pathol., November 1, 2005; 167(5): 1429 - 1442. [Abstract] [Full Text] [PDF]

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