title: Thrombin activatable fibrinolysis inhibitor.
abstract: Thrombin activatable fibrinolysis inhibitor (TAFI) was discovered two decades ago as a consequence of the identification of an unstable carboxypeptidase (CPU), which was formed upon thrombin activation of the respective pro-enzyme (proCPU). The antifibrinolytic function of the activated form (TAFIa, CPU) is directly linked to its capacity to remove C-terminal lysines from the surface of the fibrin clot. No endogenous inhibitors have been identified, but TAFIa activity is regulated by its intrinsic temperature-dependent instability with a half-life of 8 to 15 min at 37 °C. A variety of studies have demonstrated a role for TAFI/TAFIa in venous and arterial diseases. In addition, a role in inflammation and cell migration has been shown. Since an elevated level of TAFIa it is a potential risk factor for thrombotic disorders, many inhibitors, both at the level of activation or at the level of activity, have been developed and were proven to exhibit a profibrinolytic effect in animal models. Pharmacologically active inhibitors of the TAFI/TAFIa system may open new ways for the prevention of thrombotic diseases or for the establishment of adjunctive treatments during thrombolytic therapy.
authors.affiliation: Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, Leuven, Belgium. paul.declerck@pharm.kuleuven.be
authors.forename: P J
authors.initials: PJ
authors.lastname: Declerck
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000276:immunology*; D025901:Carboxypeptidase B2 / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D006487:Hemostasis / Q000276:immunology*; D006801:Humans; D010447:Peptide Hydrolases / Q000276:immunology*; D013927:Thrombosis / Q000276:immunology*
chemical_list: D010447:Peptide Hydrolases; D025901:Carboxypeptidase B2