Konings, J, Hoving, LR, Ariens, RS orcid.org/0000-0002-6310-5745 et al. (7 more authors) (2015) The role of activated coagulation factor XII in overall clot stability and fibrinolysis. Thrombosis Research, 136 (2). pp. 474-480. ISSN 0049-3848
Abstract
Activated coagulation factor XII (α-FXIIa) is able to bind to fibrin(ogen) and increases the density and stiffness of the fibrin clot. Conversely, proteins of the contact system and the fibrinolytic system show a high degree of homology and α-FXIIa can convert plasminogen into plasmin resulting in fibrin degradation. Therefore, we studied the contribution of α-FXIIa to overall clot stability and plasmin driven fibrinolysis in the absence and presence of tissue plasminogen activator (tPA).
We observed that α-FXIIa directly converted plasminogen into plasmin and reduced clot lysis time at all tPA concentrations tested (15–1500 pM). Simultaneous assessment of plasmin generation (chromogenic substrate S-2251) and fibrin formation and degradation (absorbance at 405 nm), showed an earlier onset of fibrinolysis and plasmin formation in the presence of α-FXIIa. Fibrinolysis of clots formed under flow conditions, revealed that incorporation of α-FXIIa accelerated clot breakdown (fluorescence release of labeled fibrin) by additional plasmin generation on top of formation by tPA. Scanning electron microscopy (SEM) revealed that the surface area pore size increased in the presence compared with the absence of α-FXIIa when fibrinolysis was initiated by the conversion of plasminogen with tPA during clot formation.
α-FXIIa enhances fibrinolysis in the presence of plasminogen, irrespective of whether tPA was present during clot formation or was added afterwards to initiate fibrinolysis. We postulate that FXIIa first strengthens the clot structure during clot formation and thereafter contributes towards fibrinolysis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Fibrinolysis; Tissue plasminogen activator (tPA); Fibrin(ogen); Coagulation factor XII; Blood coagulation; Clot structure |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Dec 2018 14:40 |
Last Modified: | 03 Jan 2019 15:29 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.thromres.2015.06.028 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:137908 |