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Blood, 23 April 2009, Vol. 113, No. 17, pp. 4101-4109. Prepublished online as a Blood First Edition Paper on February 20, 2009; DOI 10.1182/blood-2008-12-194258. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-12-194258v1 113/17/4101    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 Redecha, P. Articles by Girardi, G. Search for Related Content PubMed PubMed Citation Articles by Redecha, P. Articles by Girardi, G. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury Patricia Redecha1, Nico van Rooijen2, Donald Torry3, and Guillermina Girardi1 1 Department of Medicine, Weill Medical College at Cornell University, New York, NY; 2 Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands; and 3 Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield Pregnancy loss and intrauterine growth restriction (IUGR) are serious pregnancy complications, and the triggers and mediators of placental and fetal damage are not completely understood. Using a mouse model of recurrent spontaneous miscarriages (DBA/2-mated CBA/J mice) that shares features with human recurrent miscarriage and fetal growth restriction, we identified tissue factor (TF) as an essential participating factor in placental and fetal injury. We have previously shown that C5a releases antiangiogenic molecule sFlt-1 in monocytes that causes defective placental development and fetal death in DBA/2-mated CBA/J mice. In this study, we found that TF not only activates the coagulation pathway, but it also mediates sFlt-1 release in monocytes causing defective placental development and fetal death. Blockade of TF with a monoclonal antibody inhibited sFlt-1 release, prevented the pathological activation of the coagulation pathway, restored placental blood flow, prevented placental oxidative stress, and rescued pregnancies. We also demonstrated that pravastatin, by down-regulating TF expression on monocytes and trophoblasts, prevented placental damage and protected pregnancies in DBA/2-mated CBA/J mice. These studies indicate that TF is an important mediator in fetal death and growth restriction and that statins may be a good treatment for women with recurrent miscarriages and IUGR. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Poovassery, D. Sarr, G. Smith, T. Nagy, and J. M. Moore Malaria-Induced Murine Pregnancy Failure: Distinct Roles for IFN-{gamma} and TNF J. Immunol., October 15, 2009; 183(8): 5342 - 5349. [Abstract] [Full Text] [PDF]

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