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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2777-2782. Prepublished online as a Blood First Edition Paper on December 14, 2004; DOI 10.1182/blood-2004-09-3724. This Article Full Text (PDF) All Versions of this Article: 2004-09-3724v1 105/7/2777    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 Pedersen, B. Articles by Mackman, N. Search for Related Content PubMed PubMed Citation Articles by Pedersen, B. Articles by Mackman, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 28, 2004 Accepted December 9, 2004 A balance between tissue factor and tissue factor pathway inhibitor is required for embryonic development and hemostasis in adult mice Brian Pedersen, Todd Holscher, Yuichiro Sato, Rafal Pawlinski, and Nigel Mackman* Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA * Corresponding author; email: nmackman{at}scripps.edu. Inactivation of the murine tissue factor (TF) gene or tissue factor pathway inhibitor 1 (TFPI) gene results in embryonic lethality, indicating that both are required for embryonic development. We have shown that expression of low levels of TF from a transgene (hTF) rescues TF null embryos. However, low TF mice (mTF-/-/hTF+) have hemostatic defects in the uterus, placenta, heart and lung. In this study, we hypothesized that the death of TFPI-/- embryos was due to unregulated TF:FVIIa activity and that the hemostatic defects in low TF mice were due to insufficient TF expression. Therefore, we attempted to rescue TFPI-/- embryos by reducing TF expression and to restore hemostasis in low TF mice by abolishing TFPI expression. Intercrossing TFPI+/-/mTF+/-/hTF+/- mice generated close to the expected number of TFPI-/-/low TF mice at wean from 128 offspring, indicating rescue of TFPI-/- embryos from embryonic lethality. Conversely, a decrease in TFPI levels dose-dependently prolonged the survival of low TF mice and rescued the hemorrhagic defects in the lung and placenta but not in the heart or uterus. These results indicate that the correct balance between TF and TFPI in different organs is required to maintain hemostasis during embryonic development and in adult mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Breitenstein, S.F. Stampfli, G.G. Camici, A. Akhmedov, H.R. Ha, F. Follath, A. Bogdanova, T.F. Luscher, and F.C. Tanner Amiodarone Inhibits Arterial Thrombus Formation and Tissue Factor Translation Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2231 - 2238. [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] R. Sood, S. Kalloway, A. E. Mast, C. J. Hillard, and H. Weiler Fetomaternal cross talk in the placental vascular bed: control of coagulation by trophoblast cells Blood, April 15, 2006; 107(8): 3173 - 3180. [Abstract] [Full Text] [PDF] H. Weiler It's the trophoblast! Blood, October 15, 2005; 106(8): 2603 - 2603. [Full Text] [PDF]

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