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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3883-3891. Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-09-3780. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3780v1 107/10/3883    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 Iwaki, T. Articles by Castellino, F. J. Search for Related Content PubMed PubMed Citation Articles by Iwaki, T. Articles by Castellino, F. J. Related Collections Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A fibrinogen deficiency accelerates the initiation of LDL cholesterol–driven atherosclerosis via thrombin generation and platelet activation in genetically predisposed mice Takayuki Iwaki, Mayra J. Sandoval-Cooper, Markus Brechmann, Victoria A. Ploplis, and Francis J. Castellino From the W. M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN. Mice with combined deficiencies of the low-density lipoprotein receptor (LDLR–/–) and the catalytic component of an apolipoprotein B–edisome complex (APOBEC1–/–) that converts apoB-100 to apoB-48 have been characterized, and this model of LDL cholesterol–driven atherosclerosis was applied to an investigation of the role of fibrinogen (Fg) in the genesis and progression of the plaque. LDLR–/–/APOBEC1–/–/FG–/– (L–/–/A–/–/FG–/–) triple-deficient mice presented more advanced plaque in their aortic trees and aortic sinuses at 24, 36, and 48 weeks of age compared to L–/–/A–/– mice, a feature that may result from enhanced platelet activation in these former mice. This is supported by the presence of hypercoagulability, increased CD61 and CD62P on resting platelets, and higher plasma soluble P-selectin in L–/–/A–/–/FG–/– mice as compared to L–/–/A–/–, FG–/–, or wild-type mice. The elevated higher molecular weight forms of von Willebrand factor (VWF) in L–/–/A–/–/FG–/– mice, revealed by increased VWF collagen binding activity, perhaps resulting from down-regulation of its cleaving metalloproteinase, ADAMTS13, further indicates enhanced platelet activation. Thus, the earlier arterial plaque deposition in L–/–/A–/–/FG–/– mice appears to contain a contribution from enhanced levels of thrombin and activated platelets, a synergistic consequence of an Fg deficiency combined with a high LDL cholesterol concentration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Shinagawa, J. A. Martin, V. A. Ploplis, and F. J. Castellino Coagulation Factor Xa Modulates Airway Remodeling in a Murine Model of Asthma Am. J. Respir. Crit. Care Med., January 15, 2007; 175(2): 136 - 143. [Abstract] [Full Text] [PDF]

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