Thrombin‐activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)

Summary.  Recently, a new inhibitor of fibrinolysis was described, which downregulated fibrinolysis after it was activated by thrombin, and was therefore named TAFI (thrombin‐activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI turned out to be identical to the previously described proteins, procarboxypeptidase U, procarboxypeptidase R, and plasma procarboxypeptidase B. Activated TAFI (TAFIa) downregulates fibrinolysis by the removal of carboxy‐terminal lysines from fibrin. These carboxy‐terminal lysines are exposed upon limited proteolysis of fibrin by plasmin and act as ligands for the lysine‐binding sites of plasminogen and tissue‐type plasminogen activator (t‐PA). Elimination of these lysines by TAFIa abrogates the fibrin cofactor function of t‐PA‐mediated plasminogen activation, resulting in a decreased rate of plasmin generation and thus downregulation of fibrinolysis. In this review, the characteristics of TAFI are summarized, with an emphasis on the pathways leading to activation of TAFI and the role of TAFIa in the inhibition of fibrinolysis. However, it cannot be ruled out that TAFI has other, as yet undefined, functions in biology.

[1]  I. B. Borel Rinkes,et al.  Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin‐activatable fibrinolysis inhibitor , 2003, Journal of thrombosis and haemostasis : JTH.

[2]  Els Brouwers,et al.  Development of a Genotype 325–Specific proCPU/TAFI ELISA , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[3]  D. Eaton,et al.  In vivo regulation of plasminogen function by plasma carboxypeptidase B. , 2002, The Journal of clinical investigation.

[4]  Baldomero Oliva,et al.  Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI). , 2002, Journal of molecular biology.

[5]  P. Dawson,et al.  Plasmin-mediated activation and inactivation of thrombin-activatable fibrinolysis inhibitor. , 2002, Biochemistry.

[6]  M. Margaglione,et al.  Plasma Thrombin-Activatable Fibrinolysis Inhibitor Antigen Concentration and Genotype in Relation to Myocardial Infarction in the North and South of Europe , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[7]  J. Meijers,et al.  Role of zinc ions in activation and inactivation of thrombin-activatable fibrinolysis inhibitor. , 2002, Biochemistry.

[8]  M. Boffa,et al.  Two Naturally Occurring Variants of TAFI (Thr-325 and Ile-325) Differ Substantially with Respect to Thermal Stability and Antifibrinolytic Activity of the Enzyme* , 2002, The Journal of Biological Chemistry.

[9]  J. Meijers,et al.  The Role of Protein S in the Activation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and Regulation of Fibrinolysis , 2001, Thrombosis and Haemostasis.

[10]  H. Nieuwenhuis,et al.  The Defective Down Regulation of Fibrinolysis in Haemophilia A Can Be Restored by Increasing the TAFI Plasma Concentration , 2001, Thrombosis and Haemostasis.

[11]  M. Elisen,et al.  Protein C Inhibitor Regulates the Thrombin-Thrombomodulin Complex in the Up- and Down Regulation of TAFI Activation , 2001, Thrombosis and Haemostasis.

[12]  D. Tregouet,et al.  Combined segregation-linkage analysis of plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels with TAFI gene polymorphisms , 2001, Human Genetics.

[13]  G. Tosato.  A severe illness associated with EBV infection of T and NK cells , 2001 .

[14]  L. Tiret,et al.  Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled. , 2001, Blood.

[15]  J. Meijers,et al.  Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). , 2001, Thrombosis research.

[16]  J. Weitz,et al.  Thrombin-activable Fibrinolysis Inhibitor Attenuates (DD)E-mediated Stimulation of Plasminogen Activation by Reducing the Affinity of (DD)E for Tissue Plasminogen Activator , 2000, The Journal of Biological Chemistry.

[17]  A. Hamsten,et al.  Plasma Procarboxypeptidase U in Men with Symptomatic Coronary Artery Disease , 2000, Thrombosis and Haemostasis.

[18]  S. Bunting,et al.  Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and hemostasis , 2000 .

[19]  F. Rosendaal,et al.  High levels of factor IX increase the risk of venous thrombosis. , 2000, Blood.

[20]  P. Verhallen,et al.  An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. , 2000, Thrombosis research.

[21]  M. Boffa,et al.  Roles of Thermal Instability and Proteolytic Cleavage in Regulation of Activated Thrombin-activable Fibrinolysis Inhibitor* , 2000, The Journal of Biological Chemistry.

[22]  J. Griffin,et al.  Inactivation of Active Thrombin-activable Fibrinolysis Inhibitor Takes Place by a Process That Involves Conformational Instability Rather Than Proteolytic Cleavage* , 2000, The Journal of Biological Chemistry.

[23]  F. Rosendaal,et al.  High levels of coagulation factor XI as a risk factor for venous thrombosis. , 2000, The New England journal of medicine.

[24]  J. Meijers,et al.  Reduced activity of TAFI (thrombin‐activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia , 2000, British journal of haematology.

[25]  F. Goossens,et al.  Proteolytic activation of purified human procarboxypeptidase U. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[26]  J. Shafer,et al.  Characterization of Plasmin-mediated Activation of Plasma Procarboxypeptidase B , 1999, The Journal of Biological Chemistry.

[27]  M. Boffa,et al.  Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B). , 1999, Biochemistry.

[28]  F. Avilés,et al.  A Carboxypeptidase Inhibitor from the Medical Leech Hirudo medicinalis , 1998, The Journal of Biological Chemistry.

[29]  M. Nagashima,et al.  Identification and Characterization of Two Thrombin-activatable Fibrinolysis Inhibitor Isoforms , 1998, Thrombosis and Haemostasis.

[30]  P. A. von dem Borne,et al.  Plasma TAFI Levels Influence the Clot Lysis Time in Healthy Individuals in the Presence of an Intact Intrinsic Pathway of Coagulation , 1998, Thrombosis and Haemostasis.

[31]  M. Boffa,et al.  A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor* , 1998, The Journal of Biological Chemistry.

[32]  P. A. von dem Borne,et al.  Factor XI and Protection of the Fibrin Clot against Lysis – a Role for the Intrinsic Pathway of Coagulation in Fibrinolysis , 1998, Thrombosis and Haemostasis.

[33]  K. Kokame,et al.  Activation of Thrombin-activable Fibrinolysis Inhibitor Requires Epidermal Growth Factor-like Domain 3 of Thrombomodulin and Is Inhibited Competitively by Protein C* , 1998, The Journal of Biological Chemistry.

[34]  M. Boffa,et al.  Plasma and Recombinant Thrombin-activable Fibrinolysis Inhibitor (TAFI) and Activated TAFI Compared with Respect to Glycosylation, Thrombin/Thrombomodulin-dependent Activation, Thermal Stability, and Enzymatic Properties* , 1998, The Journal of Biological Chemistry.

[35]  E. Plow,et al.  On the Mechanism of the Antifibrinolytic Activity of Plasma Carboxypeptidase B* , 1997, The Journal of Biological Chemistry.

[36]  P. A. von dem Borne,et al.  Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. , 1997, The Journal of clinical investigation.

[37]  G. Broze,et al.  Coagulation-dependent inhibition of fibrinolysis: role of carboxypeptidase-U and the premature lysis of clots from hemophilic plasma. , 1996, Blood.

[38]  M. Nesheim,et al.  The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. , 1996, Blood.

[39]  J. Morser,et al.  TAFI, or Plasma Procarboxypeptidase B, Couples the Coagulation and Fibrinolytic Cascades through the Thrombin-Thrombomodulin Complex* , 1996, The Journal of Biological Chemistry.

[40]  J. Enghild,et al.  Activated Human Plasma Carboxypeptidase B Is Retained in the Blood by Binding to α2-Macroglobulin and Pregnancy Zone Protein* , 1996, The Journal of Biological Chemistry.

[41]  E. Topol,et al.  Inducible carboxypeptidase activity. A role in clot lysis in vivo. , 1996, Circulation.

[42]  D. Eaton,et al.  Plasma carboxypeptidases as regulators of the plasminogen system. , 1995, The Journal of clinical investigation.

[43]  P. A. von dem Borne,et al.  Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. , 1995, Blood.

[44]  D. Rijken,et al.  Superficial accumulation of plasminogen during plasma clot lysis. , 1995, Circulation.

[45]  M. Nesheim,et al.  Purification and Characterization of TAFI, a Thrombin-activable Fibrinolysis Inhibitor (*) , 1995, The Journal of Biological Chemistry.

[46]  D. Eaton,et al.  Activation and characterization of procarboxypeptidase B from human plasma. , 1995, Biochemistry.

[47]  J. Vandenbroucke,et al.  Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis , 1995, The Lancet.

[48]  D. Hendriks,et al.  Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen. , 1994, The Journal of biological chemistry.

[49]  B. Brenner,et al.  Dental surgery in patients with severe factor XI deficiency without plasma replacement. , 1992, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[50]  D. Drayna,et al.  Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. , 1991, The Journal of biological chemistry.

[51]  G. Broze,et al.  Factor XI activation in a revised model of blood coagulation , 1991, Science.

[52]  E. Angles-cano,et al.  Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines. , 1991, Biochemistry.

[53]  E. Davie,et al.  Factor XI deficiency in Ashkenazi Jews in Israel. , 1991, The New England journal of medicine.

[54]  K Fujikawa,et al.  Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. , 1991, The Journal of biological chemistry.

[55]  S. Scharpe,et al.  Purification and characterization of a new arginine carboxypeptidase in human serum. , 1990, Biochimica et biophysica acta.

[56]  H. Okada,et al.  An arginine specific carboxypeptidase generated in blood during coagulation or inflammation which is unrelated to carboxypeptidase N or its subunits. , 1989, Biochemical and biophysical research communications.

[57]  U. Christensen.  C‐terminal lysine residues of fibrinogen fragments essential for binding to plasminogen , 1985, FEBS Letters.

[58]  M. Hoylaerts,et al.  Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. , 1982, The Journal of biological chemistry.

[59]  E. Erdos,et al.  An enzyme in human blood plasma that inactivates bradykinin and kallidins. , 1962, Biochemical pharmacology.

[60]  M. Halks-Miller,et al.  Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. , 2002, The Journal of clinical investigation.

[61]  J. Meijers,et al.  Regulation of Fibrinolysis in Plasma by TAFI and Protein C Is Dependent on the Concentration of Thrombomodulin , 2001, Thrombosis and Haemostasis.

[62]  P. Reitsma,et al.  Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis. , 2001, Haematologica.

[63]  P. Klement,et al.  A Novel Approach to Arterial Thrombolysis , 1999 .

[64]  C. Hack,et al.  Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor. , 1998, The Journal of clinical investigation.

[65]  S. Scharpe,et al.  Characterisation of a Carboxypeptidase in Human Serum Distinct from Carboxypeptidase N , 1989, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[66]  V. Kunzmann,et al.  A novel , possibly functional , single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor ( TAFI ) gene is also associated with TAFI levels , 2022 .