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Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Theme Issue
New oral anticoagulants for stroke prevention in atrial fibrillation

DOI: https://doi.org/10.1160/TH13-10-0855
Issue: 2014: 111/5(May) pp. 781-1006
Pages: 842-850
Ahead of Print: 2014-01-16

Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function

Online Supplementary Material

C. Duval (1), P. Allan (1, 2), S. D. A. Connell (2), V. C. Ridger (3), H. Philippou (1), R. A. S. Ariëns (1)

(1) Theme Thrombosis, Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics and Multidisciplinary Cardiovascular Research Centre, Faculty of Medicine and Health, University of Leeds, UK; (2) Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, UK; (3) Department of Cardiovascular Science, Faculty of Medicine, Dentistry, and Health, University of Sheffield, UK

Keywords

fibrinogen, factor XIII, clot structure

Summary

Factor XIII is responsible for the cross-linking of fibrin γ-chains in the early stages of clot formation, whilst α-chain cross-linking occurs at a slower rate. Although γ- and α-chain cross-linking was previously shown to contribute to clot stiffness, the role of cross-linking of both chains in determining clot structure is currently unknown. Therefore, the aim of this study was to determine the role of individual α- and γ-chain cross-linking during clot formation, and its effects on clot structure. We made use of a recombinant fibrinogen (γQ398N/Q399N/K406R), which does not allow for γ-chain cross-linking. In the absence of cross-linking, intact D-D interface was shown to play a potential role in fibre appearance time, clot stiffness and elasticity. Cross-linking of the fibrin α-chain played a role in the thickening of the fibrin fibres over time, and decreased lysis rate in the absence of α2-antiplasmin. We also showed that α-chain cross-linking played a role in the timing of fibre appearance, straightening fibres, increasing clot stiffness and reducing clot deformation. Cross-linking of the γ-chain played a role in fibrin fibre appearance time and fibre density. Our results show that α- and γ-chain cross-linking play independent and specific roles in fibrin clot formation and structure.

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