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• W2051581796 abstract "During fibrinolysis, tissue-type plasminogen activator (t-PA)-mediated plasmin generation leads to degradation of fibrin into fibrin degradation products (FDP) resulting in blood clot dissolution. Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) retards fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin, thereby attenuating its cofactor function in the t-PA-mediated plasmin generation [ [1] Bajzar L. Morser J. Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. J Biol Chem. 1996; 271: 16603-16608 Crossref PubMed Scopus (588) Google Scholar ]. In vivo evidence for a role of TAFI in fibrinolysis has been obtained in several animal models through pharmacological inhibition and gene-deletion [ 2 Nagashima M. Werner M. Wang M. Zhao L. Light D.R. Pagila R. et al. An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. Thromb Res. 2000; 98: 333-342 Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar , 3 Klement P. Liao P. Bajzar L. A novel approach to arterial thrombolysis. Blood. 1999; 94: 2735-2743 Crossref PubMed Google Scholar , 4 Vercauteren E. Emmerechts J. Peeters M. Hoylaerts M.F. Declerck P.J. Gils A. Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model. Blood. 2011; 117: 4615-4622 Crossref PubMed Scopus (36) Google Scholar , 5 Vercauteren E. Peeters M. Hoylaerts M.F. Lijnen H.R. Meijers J.C. Declerck P.J. et al. The hyperfibrinolytic state of mice with combined thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 gene deficiency is critically dependent on TAFI deficiency. J Thromb Haemost. 2012; 10: 2555-2562 Crossref PubMed Scopus (20) Google Scholar , 6 Binette T.M. Taylor Jr., F.B. Peer G. Bajzar L. Thrombin-thrombomodulin connects coagulation and fibrinolysis: more than an in vitro phenomenon. Blood. 2007; 110: 3168-3175 Crossref PubMed Scopus (56) Google Scholar , 7 te Velde E.A. Wagenaar G.T. Reijerkerk A. Roose-Girma M. Borel Rinkes I.H. Voest E.E. et al. Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor. J Thromb Haemost. 2003; 1: 2087-2096 Crossref PubMed Scopus (76) Google Scholar ]. The amino acid sequence of mouse TAFI shares approximately 85% identity with human TAFI including conservation of important residues involved in glycosylation, zinc binding, substrate binding and substrate specificity. TAFI from both species also have similar biochemical characteristics with respect to their activatability by the thrombin/thrombomodulin (T/TM) complex and their antifibrinolytic effect during in vitro clot lysis [ 8 Hillmayer K. Macovei A. Pauwels D. Compernolle G. Declerck P.J. Gils A. Characterization of rat thrombin-activatable fibrinolysis inhibitor (TAFI)—a comparative study assessing the biological equivalence of rat, murine and human TAFI. J Thromb Haemost. 2006; 4: 2470-2477 Crossref PubMed Scopus (19) Google Scholar , 9 Schatteman K.A. Goossens F.J. Scharpé S.S. Hendriks D.F. Activation of plasma procarboxypeptidase U in different mammalian species points to a conserved pathway of inhibition of fibrinolysis. Thromb Haemost. 1999; 82: 1718-1721 Crossref PubMed Scopus (36) Google Scholar ]. Addition of human TAFI to mouse TAFI depleted plasma has a more pronounced effect compared to addition of mouse TAFI in retarding clot lysis [ [8] Hillmayer K. Macovei A. Pauwels D. Compernolle G. Declerck P.J. Gils A. Characterization of rat thrombin-activatable fibrinolysis inhibitor (TAFI)—a comparative study assessing the biological equivalence of rat, murine and human TAFI. J Thromb Haemost. 2006; 4: 2470-2477 Crossref PubMed Scopus (19) Google Scholar ]. Recently, transgenic mice devoid of mouse TAFI but expressing human TAFI (hTAFI) were generated [ [10] Valls Seron M. Thrombin-Activatable Fibrinolysis Inhibitor and Bacterial Infections. Experimental Vascular Medicine. UvA-DARE, the institutional repository of the University of Amsterdam (UvA): University of Amsterdam, 2011: 128 Google Scholar ]. In the present study, we studied the fibrinolytic capacity in hTAFI mice using both in vitro and in vivo models. The aim of the study was to establish model systems in which the effect of TAFI inhibitors exclusively targeting human TAFI could be tested." @default.
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• W2051581796 date "2014-06-01" @default.
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• W2051581796 title "Clot stability and fibrin deposition is strongly reduced in mice in which mouse TAFI is replaced by human TAFI" @default.
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