OBJECTIVE: To review the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and activity of activated TAFI (TAFIa) as it relates to the regulation of both fibrinolytic and proinflammatory substances. DATA SOURCE: Published articles and reviews (from PubMed, published between 1962 and 2003) on experimental studies of coagulation, fibrinolysis, and inflammation. DATA SYNTHESIS AND CONCLUSIONS: The principal physiologic role of TAFI is still a matter of debate. Although TAFI activation can result from proteolysis by a number of proteases, the most likely physiologic activators are thrombin (in complex with the cofactor thrombomodulin) and plasmin (in complex with polysaccharide cofactors). The activated enzyme, TAFIa, displays carboxypeptidase B-like activity and probably regulates both fibrinolysis and inflammation in response to injury and infection. At present, there is limited understanding of the role that TAFI plays in the interrelationships between coagulation, fibrinolysis, and inflammation. Although the potential therapeutic value of TAFIa inhibition/TAFI activation awaits further investigation, the data gathered to date suggest that, like activated protein C, TAFIa may play a pivotal role in regulating the crosstalk between coagulation, fibrinolysis, and inflammation.
OBJECTIVE: To review the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and activity of activated TAFI (TAFIa) as it relates to the regulation of both fibrinolytic and proinflammatory substances. DATA SOURCE: Published articles and reviews (from PubMed, published between 1962 and 2003) on experimental studies of coagulation, fibrinolysis, and inflammation. DATA SYNTHESIS AND CONCLUSIONS: The principal physiologic role of TAFI is still a matter of debate. Although TAFI activation can result from proteolysis by a number of proteases, the most likely physiologic activators are thrombin (in complex with the cofactor thrombomodulin) and plasmin (in complex with polysaccharide cofactors). The activated enzyme, TAFIa, displays carboxypeptidase B-like activity and probably regulates both fibrinolysis and inflammation in response to injury and infection. At present, there is limited understanding of the role that TAFI plays in the interrelationships between coagulation, fibrinolysis, and inflammation. Although the potential therapeutic value of TAFIa inhibition/TAFI activation awaits further investigation, the data gathered to date suggest that, like activated protein C, TAFIa may play a pivotal role in regulating the crosstalk between coagulation, fibrinolysis, and inflammation.
Authors: Stephanie A Smith; Nicola J Mutch; Deepak Baskar; Peter Rohloff; Roberto Docampo; James H Morrissey Journal: Proc Natl Acad Sci U S A Date: 2006-01-12 Impact factor: 11.205