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Blood, 1 August 2007, Vol. 110, No. 3, pp. 902-907. Prepublished online as a Blood First Edition Paper on April 13, 2007; DOI 10.1182/blood-2007-01-066837. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-066837v1 110/3/902    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 Standeven, K. F Articles by Ariens, R. A. Search for Related Content PubMed PubMed Citation Articles by Standeven, K. F Articles by Ariens, R. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 12, 2007 Accepted April 12, 2007 Functional analysis of fibrin -chain cross-linking by activated factor XIII: determination of a cross-linking pattern that maximises clot stiffness Kristina F Standeven, Angela Maria Carter, Peter J Grant*, John W Weisel, Irina Chernysh, Leona Masova, Susan T Lord, and Robert AS Ariens Academic Unit of Molecular Vascular Medicine, Leeds Inst. for Genetics Health & Therapeutics, Faculty of Medicine & Health, University of Leeds, Leeds, United Kingdom Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, United States * Corresponding author; email: p.j.grant{at}leeds.ac.uk. Activated coagulation factor XIII (FXIIIa) cross-links the -chains of fibrin early in clot formation. Cross-linking of the -chains occurs more slowly, leading to high molecular weight multimer formations that can also contain -chains. To study the contribution of FXIIIa-induced -chain cross-linking on fibrin structure and function, we created two recombinant fibrinogens (Q398N/Q399N/K406R and K406R) that modify the -chain cross-linking process. In K406R, -dimer cross-links were absent, but FXIIIa produced a cross-linking pattern similar to that observed in tissue transglutaminase cross-linked fibrin(ogen) with mainly - cross-links. In Q398N/Q399N/K406R, cross-links with any -chain involvement were completely absent, and only -chain cross-linking occurred. Upon cross-linking, recombinant normal fibrin yielded a 3.5-fold increase in stiffness, compared with a 2.5-fold increase by -chain cross-linking alone (Q398N/Q399N/K406R). K406R fibrin showed a 1.5-fold increase in stiffness after cross-linking. No major differences in clot morphology, polymerisation and lysis rates were observed, although fibre diameter was slightly lower in cross-linked normal fibrin relative to the variants. Our results show that -chain cross-linking contributes significantly to clot stiffness, in particular through -dimer formation; - hybrid cross-links had the smallest impact on clot stiffness. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. T. O'Brien III, M. R. Falvo, D. Millard, B. Eastwood, R. M. Taylor II, and R. Superfine Ultrathin self-assembled fibrin sheets PNAS, December 9, 2008; 105(49): 19438 - 19443. [Abstract] [Full Text] [PDF]

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