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Blood, 15 January 2008, Vol. 111, No. 2, pp. 643-650. Prepublished online as a Blood First Edition Paper on October 9, 2007; DOI 10.1182/blood-2007-05-091231. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-091231v1 111/2/643    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 Ajjan, R. Articles by Ariens, R. A. Search for Related Content PubMed PubMed Citation Articles by Ajjan, R. Articles by Ariens, R. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 21, 2007 Accepted September 24, 2007 Common variation in the C-terminal region of the fibrinogen -chain: effects on fibrin structure, fibrinolysis and clot rigidity Ramzi Ajjan, Bernard CB Lim, Kristina F Standeven, Robert Harrand, Sarah Dolling, Fladia Phoenix, Richard Greaves, Radwa H Abu-Saleh, Simon Connell, David AM Smith, John W Weisel, Peter J. Grant*, and Robert AS Ariens Academic Unit of Molecular Vascular Medicine, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA, United States Department of Physics, University of Leeds, Leeds, United Kingdom Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom * Corresponding author; email: p.j.grant{at}leeds.ac.uk. Fibrinogen BArg448Lys is a common polymorphism, positioned within the carboxyl terminus of the B-chain of the molecule. Studies suggest that it is associated with severity of coronary artery disease and development of stroke. The effects of the amino acid substitution on clot structure remains controversial and the aim of this study was to investigate the effect(s) of this polymorphism on fibrin clot structure using recombinant techniques. Permeation, turbidity and scanning electron microscopy showed that recombinant Lys448 fibrin had a significantly more compact structure, with thin fibres and small pores compared with Arg448. Clot stiffness, measured using a novel method employing magnetic tweezers, was significantly higher for the Lys448 compared to Arg448 variant. Clots made from recombinant protein variants had similar lysis rate outside plasma environment but when added to fibrinogen-depleted plasma, fibrinolysis rate for Lys448 were significantly slower compared with Arg448. This study demonstrates, for the first time, that clots made from recombinant BLys448 fibrinogen are characterized by thin fibres and small pores, show increased stiffness and are more resistant to fibrinolysis. Fibrinogen BArg448Lys is a primary example of common genetic variation with a significant phenotypic effect at the molecular level. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R.A. Ajjan, K.F. Standeven, M. Khanbhai, F. Phoenix, K.C. Gersh, J.W. Weisel, M.T. Kearney, R.A.S. Ariens, and P.J. Grant Effects of Aspirin on Clot Structure and Fibrinolysis Using a Novel In Vitro Cellular System Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 712 - 717. [Abstract] [Full Text] [PDF]

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