Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles.
The thrombin-activatable fibrinolysis inhibitor (TAFI) pathway defines a novel molecular connection between blood coagulation and both fibrinolysis and inflammation. TAFI is a plasma zymogen that can be activated by thrombin, the thrombin-thrombomodulin complex, or plasmin. The activated form of TAFI (TAFIa) attenuates fibrinolysis by removing the carboxyl-terminal lysine residues from partially degraded fibrin that mediate positive feedback in the fibrinolytic cascade. A role for TAFIa in modulating inflammation is suggested by the ability of this enzyme to down-regulate pericellular plasminogen activation and to inactivate the inflammatory peptides bradykinin and the anaphylatoxins C3a and C5a. The focus of this review is on recent advances in the clinical measurement of the TAFI pathway in human subjects and what this has revealed in terms of the molecular genetics of TAFI, the biological variation in plasma TAFI antigen levels, potential regulators of expression of the gene encoding TAFI, and the TAFI pathway as a risk factor for the development of vascular diseases. Although this field is in its infancy, much recent progress has been made and the available data suggest that the TAFI pathway is an intriguing new player in a variety of physiological and pathophysiological contexts.
Boffa
Michael B
MB
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6. boffam@post.queensu.ca
Koschinsky
Marlys L
ML
D000818:Animals; D025901:Carboxypeptidase B2 / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D025901:Carboxypeptidase B2