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Blood, 15 March 2004, Vol. 103, No. 6, pp. 1995-2002. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-10-3401. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: 2003-10-3401v1 103/6/1995    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 Jirouskova, M. Articles by Coller, B. S Search for Related Content PubMed PubMed Citation Articles by Jirouskova, M. Articles by Coller, B. S Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 3, 2003 Accepted November 6, 2003 Antibody blockade or mutation of the fibrinogen chain C-terminus are more effective in inhibiting murine arterial thrombus formation than complete absence of fibrinogen Marketa Jirouskova*, Igor Chereshnev, Heikki Vaananen, Jay L Degen, and Barry S Coller Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY, USA Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY, USA Children's Hospital Medical Center, Cincinnati, OH, none * Corresponding author; email: marketa{at}rockefeller.edu. Elevated plasma fibrinogen is a risk factor for thrombotic cardiovascular disease, but which of fibrinogen's functions is responsible for the increased risk is unknown. To define better the contribution of fibrinogen to large vessel thrombus formation, we studied carotid artery thrombosis in wild-type mice, mice lacking fibrinogen (fbg -/-), mice treated with 7E9 (a blocking antibody to the fibrinogen chain C-terminus), and mice expressing a mutant fibrinogen (5) that lacks the chain platelet binding motif QADGV. In control mice, thrombus formation resulted in occlusion in 8 ± 2 min (mean ± SD). In fbg -/- mice, thrombi grew to large sizes, but then they abruptly embolized, confirming previous observations by others in arteriolar thrombus model. In contrast, mice treated with 7E9 and 5 mice developed only small, nonoclusive mural thrombi and embolization was limited. These findings reveal that a fibrinogen antibody, 7E9, or a fibrinogen mutant retaining clotting function, can limit thrombus formation more effectively than the complete absence of fibrinogen. We hypothesize that the smaller thrombi in these animals result from the ability of fibrin to bind and sequester thrombin and/or the ability of the altered fibrinogen molecules, which cannot recruit platelets, to bind to and passivate the surface. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fibrinogen contributions to arterial thrombus formation: vessel size counts Michael W. Mosesson Blood 2004 103: 1977-1978. [Full Text] [PDF] This article has been cited by other articles: J. Ahamed, N. Burg, K. Yoshinaga, C. A. Janczak, D. B. Rifkin, and B. S. Coller In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-{beta}1 Blood, November 1, 2008; 112(9): 3650 - 3660. [Abstract] [Full Text] [PDF] S. P. Jackson The growing complexity of platelet aggregation Blood, June 15, 2007; 109(12): 5087 - 5095. [Abstract] [Full Text] [PDF] P. Stoll, N. Bassler, C. E. Hagemeyer, S. U. Eisenhardt, Y. C. Chen, R. Schmidt, M. Schwarz, I. Ahrens, Y. Katagiri, B. Pannen, et al. Targeting Ligand-Induced Binding Sites on GPIIb/IIIa via Single-Chain Antibody Allows Effective Anticoagulation Without Bleeding Time Prolongation Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1206 - 1212. [Abstract] [Full Text] [PDF] C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF] C. Nonne, N. Lenain, B. Hechler, P. Mangin, J.-P. Cazenave, C. Gachet, and F. Lanza Importance of Platelet Phospholipase C{gamma}2 Signaling in Arterial Thrombosis as a Function of Lesion Severity Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1293 - 1298. [Abstract] [Full Text] [PDF] J. S. Palumbo, K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, M. Jirouskova, and J. L. Degen Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells Blood, January 1, 2005; 105(1): 178 - 185. [Abstract] [Full Text] [PDF]

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