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Blood, 1 January 2006, Vol. 107, No. 1, pp. 132-134. Prepublished online as a Blood First Edition Paper on September 13, 2005; DOI 10.1182/blood-2005-07-2681. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2681v1 107/1/132    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smith, L. H. Articles by Vaughan, D. E. Search for Related Content PubMed PubMed Citation Articles by Smith, L. H. Articles by Vaughan, D. E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis Layton H. Smith, John D. Dixon, John R. Stringham, Mesut Eren, Hassan Elokdah, Dave L. Crandall, Kay Washington, and Douglas E. Vaughan From the Departments of Medicine and Pathology, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN; and Wyeth Research, Collegeville, PA. Hepatic veno-occlusive disease (VOD) is a common complication of high-dose chemotherapy associated with bone marrow transplantation. While the pathogenesis of VOD is uncertain, plasminogen activator inhibitor-1 (PAI-1) has emerged as a diagnostic marker and predictor of VOD in humans. In this study, we investigated the role of PAI-1 in a murine model of VOD produced by long-term nitric oxide synthase inhibition using L-NAME. After 6 weeks, wild-type (WT) mice developed extensive fibrinoid hepatic venous thrombi and biochemical evidence of hepatic injury and dysfunction. In contrast, PAI-1–deficient mice were largely protected from the development of hepatic vein thrombosis. Furthermore, WT mice that received tiplaxtinin, an antagonist of PAI-1, were effectively protected from L-NAME–induced thrombosis. Taken together, these data indicate that NO and PAI-1 play pivotal and antagonistic roles in hepatic vein thrombosis and that PAI-1 is a potential target in the prevention and treatment of VOD in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Izuhara, S. Takahashi, M. Nangaku, S. Takizawa, H. Ishida, K. Kurokawa, C. van Ypersele de Strihou, N. Hirayama, and T. Miyata Inhibition of Plasminogen Activator Inhibitor-1: Its Mechanism and Effectiveness on Coagulation and Fibrosis Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 672 - 677. [Abstract] [Full Text] [PDF] F. Milliat, J.-C. Sabourin, G. Tarlet, V. Holler, E. Deutsch, V. Buard, R. Tamarat, A. Atfi, M. Benderitter, and A. Francois Essential Role of Plasminogen Activator Inhibitor Type-1 in Radiation Enteropathy Am. J. Pathol., March 1, 2008; 172(3): 691 - 701. [Abstract] [Full Text] [PDF] W. P. Fay, N. Garg, and M. Sunkar Vascular Functions of the Plasminogen Activation System Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1231 - 1237. [Abstract] [Full Text] [PDF] N. V. Gorlatova, J. M. Cale, H. Elokdah, D. Li, K. Fan, M. Warnock, D. L. Crandall, and D. A. Lawrence Mechanism of Inactivation of Plasminogen Activator Inhibitor-1 by a Small Molecule Inhibitor J. Biol. Chem., March 23, 2007; 282(12): 9288 - 9296. [Abstract] [Full Text] [PDF] D. E. Vaughan PAI-1 and TGF-{beta}: Unmasking the Real Driver of TGF-{beta}-Induced Vascular Pathology Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 679 - 680. [Full Text] [PDF]

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