title: Thrombin activatable fibrinolysis inhibitor: at the nexus of fibrinolysis and inflammation.
abstract: TAFI (thrombin activatable fibrinolysis inhibitor) is the precursor of a basic carboxypeptidase (TAFIa) with strong antifibrinolytic and anti-inflammatory activity. Compelling evidence indicates that thrombin, either alone or in complex with thrombomodulin, is the main physiological activator of TAFI. For this reason derangements of thrombin formation, whatever the cause, may influence the fibrinolytic process too. Experimental models of thrombosis suggest that TAFI may participate in thrombus development and persistence under certain circumstances. In several models of pharmacological thrombolysis, the administration of TAFI inhibitors along with the fibrinolytic agent leads to a marked improvement of thrombus lysis, underscoring the potential of TAFI inhibitors as adjuvants for thrombolytic therapy. The role of TAFI in inflammatory diseases is more complex as it may serve as a defense mechanism, exacerbate the disease, or have no influence, depending on the nature of the model and the role played by the mediators controlled by TAFIa. Finally, the numerous clinical studies in patients with thrombotic disease support the idea that increased levels of TAFI and/or the enhancement of TAFI activation may represent a new risk factor for venous and arterial thrombosis.
authors: Department of Biomedical Sciences and Human Oncology – Section of General and Experimental Pathology, University Aldo Moro, Bari, Italy. mario.colucci@dimo.uniba.it
authors: Mario
authors: M
authors: Colucci
authors: Nicola
authors: N
authors: Semeraro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D025901:Carboxypeptidase B2 / Q000037:antagonists & inhibitors / Q000097:blood*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D013917:Thrombin / Q000378:metabolism; D015912:Thrombolytic Therapy; D018180:Thrombomodulin / Q000097:blood; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D018180:Thrombomodulin; D025901:Carboxypeptidase B2; D013917:Thrombin