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Blood, 15 July 2004, Vol. 104, No. 2, pp. 415-419. Prepublished online as a Blood First Edition Paper on March 23, 2004; DOI 10.1182/blood-2004-02-0478. This Article Full Text (PDF) All Versions of this Article: 2004-02-0478v1 104/2/415    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shim, K. Articles by Sadler, J E Search for Related Content PubMed PubMed Citation Articles by Shim, K. Articles by Sadler, J E Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2004 Accepted March 11, 2004 A recombinant murine meizothrombin precursor, prothrombin R157A/ R268A, inhibits thrombosis in a model of acute carotid artery injury Kyuhwan Shim, Hongfa Zhu, Lisa A Westfield, and J E Sadler* Department of Medicine, Department of Biochemistry and Molecular Biophysics, and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO, USA * Corresponding author; email: esadler{at}im.wustl.edu. Mutations in human prothrombin that generate a stable form of meizothrombin or meizothrombin(desF1) cause dysprothrombinemia in both the homozygous and heterozygous state, suggesting that meizothrombin has dominant anticoagulant effects in vivo. The enzymatic characterization of recombinant mouse meizothrombin, meizothrombin(desF1), and thrombin indicates that all three enzymes have similar activity toward the chromogenic substrate S-2238, that meizothrombin and meizothrombin(desF1) have <10% of the fibrinogen clotting activity of thrombin, and that meizothrombin is more active than thrombin or meizothrombin(desF1) for thrombomodulin-dependent protein C activation. Thus, activated mouse prothrombin R157A/R268A is similar to human meizothrombin in activity toward S-2238, fibrinogen, and protein C. The time-to-occlusion after FeCl3 induced carotid artery injury was delayed (11.8 ± 3.6 min, n = 5) in Cf2+/- mice infused with prothrombin R157A/R268A compared to control mice infused with wild-type prothrombin (5.3 ± 1.5 min, n = 3, P = 0.006). In this model, prothrombin R157A/R268A has anticoagulant activity that reflects its decreased fibrinogen clotting activity and preserved protein C activating activity, and is consistent with dominant inhibition of fibrinogen clotting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Anticoagulation by a thrombin precursor Sriram Krishnaswamy Blood 2004 104: 301. [Full Text] [PDF]

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