Carboxypeptidase U (TAFIa): a metallocarboxypeptidase with a distinct role in haemostasis and a possible risk factor for thrombotic disease

Judith Leurs; Dirk Hendriks

doi:10.1160/TH04-07-0454

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(03): 471-487
DOI: 10.1160/TH04-07-0454

Review Article

Schattauer GmbH

Carboxypeptidase U (TAFIa): a metallocarboxypeptidase with a distinct role in haemostasis and a possible risk factor for thrombotic disease

Judith Leurs

¹Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

,

Dirk Hendriks

¹Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

› Author Affiliations

Abstract

Summary

Since the discovery of Carboxypeptidase U (CPU) in 1988, considerable information has been gathered about its biochemistry and function in physiological and pathophysiological circumstances. A variety of tools such as assays to measure proCPU and CPU, antibodies raised against (pro)CPU, selective CPU inhibitors and knock-out mice have been developed and are currently being used to explore the role of this metallocarboxypeptidase in different in vivo and in vitro settings. The knowledge that proCPU can be activated by thrombin and plasmin, enzymes with a key function in coagulation and fibrinolysis, and the ability of CPU to remove C-terminal lysine residues has led to the hypothesis that the proCPU/CPU pathway plays a role in the balance between coagulation and fibrinolysis. The maintenance of the equilibrium between coagulation and fibrinolysis is crucial for normal haemostasis and disturbance of this delicate balance can lead either to bleeding tendency or thrombosis. This review provides an update on several aspects of CPU known at the moment, including an extensive overview on the clinical studies performed up till now.

J. Leurs is a research assistant of the Fund for Scientific Research Flanders (FWO-Vlaanderen).

Keywords

TAFI - carboxypeptidase U - fibrinolysis

Full Text

References

References
1 Hendriks D, Scharpé S, van Sande M. et al. Characterisation of a carboxypeptidase in human serum distinct from carboxypeptidase N.. J Clin Chem Clin Biochem 1989; 27: 277-85.
2 Campbell W, Okada H. An arginine specific carboxypeptidase generated in blood during coagulation or inflammation which is unrelated to carboxypeptidase N or its subunits.. Biochem Biophys Res Commun 1989; 162: 933-9.
3 Campbell W, Yonezu K, Shinohara T. et al. An arginine carboxypeptidase generated during coagulation is diminished or absent in patients with rheumatoid arthritis.. J Lab Clin Med 1990; 115: 610-2.
4 Hendriks D, Wang W, Scharpé S. et al. Purification and characterization of a new arginine carboxypeptidase in human serum.. Biochim Biophys Acta 1990; 1034: 86-92.
5 Hendriks D, Wang W, van Sande M. et al. Human serum carboxypeptidase U: a new kininase?. Agents Actions Suppl 1992; 38: 407-13.
6 Shinohara T, Sakurada C, Suzuki T. et al. Procarboxypeptidase R cleaves bradykinin following activation.. Int Arch Allergy Immunol 1994; 103: 400-4.
7 Kato K, Shinagawa N, Hayakawa T. et al. Changes in arginine carboxypeptidase (CPR) activity in stressed rats.. Pathophysiology 1994; 1: 131-6.
8 Eaton DL, Malloy BE, Tsai SP. et al. Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma.. J Biol Chem 1991; 266: 21833-8.
9 Redlitz A, Tan AK, Eaton DL. et al. Plasma carboxypeptidases as regulators of the plasminogen system.. J Clin Invest 1995; 96: 2534-8.
10 Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor.. J Biol Chem 1995; 270: 14477-84.
11 Vanhoof G, Wauters J, Schatteman K. et al. The gene for human carboxypeptidase U (CPU)–a proposed novel regulator of plasminogen activation–maps to 13q14.11.. Genomics 1996; 38: 454-5.
12 Barrett AJ. Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB). Enzyme Nomenclature. Recommendations Supplement 4: corrections and additions (1997).. Eur J Biochem 1997; 250: 1-6.
13 Rawlings ND, Barrett AJ. Evolutionary families of peptidases.. Biochem J 1993; 290: 205-18.
14 Barrett AJ, Rawlings ND, Woessner JF. Handbook of proteolytic enzymes.. San Diego: Academic Press; 1998
15 Wei SW, Segura S, Vendrell J. et al. Identification and characterization of three members of the human metallocarboxypeptidase gene family.. J Biol Chem 2002; 277: 14954-64.
16 Huang HJ, Reed CP, Zhang JS. et al. Carboxypeptidase A3 (CPA3): A novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells.. Cancer Res 1999; 59: 2981-8.
17 Wei SW, Feng Y, Kalinia E. et al. Neuropeptideprocessing carboxypeptidases.. Life Sci 2003; 73: 655-62.
18 Smulevitch SV, Osterman AL, Galperina OV. et al. Molecular cloning and primary structure of Thermoactinomyces vulgaris carboxypeptidase T. A metalloenzyme endowed with dual substrate specificity.. FEBS Lett 1991; 291: 75-8.
19 Joshi L, St Leger RJ. Cloning, expression, and substrate specificity of MeCPA, a zinc carboxypeptidase that is secreted into infected tissues by the fungal entomopathogen Metarhizium anisopliae.. J Biol Chem 1999; 274: 9803-11.
20 Barbosa Pereira PJ, Segura-Martin S, Oliva B. et al. Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI).. J Mol Biol 2002; 321: 537-47.
21 Boffa MB, Wang W, Bajzar L. 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.. J Biol Chem 1998; 273: 2127-35.
22 Boffa M. Thrombin activable fibrinolysis inhibitor (TAFI): molecular genetics of an emerging potential risk factor for thrombotic disorders.. Current Drugs Targets Cardiovas Haematol Disord 2001; 1: 59-74.
23 McDonald J. An overview of protease specificity and catalytic mechanisms: aspects related to nomenclature and classification.. Histochemical J 1985; 17: 773-85.
24 Christianson DW, Lipscomb WN, Carboxypeptidase A. Acc Chem Res. 1989: 62-9.
25 Phillips MA, Fletterick R, Rutter WJ. Arginine 127 stabilizes the transition state in carboxypeptidase.. J Biol Chem 1990; 265: 20692-8.
26 Vendrell J, Querol E, Avilés FX. Metallocarboxypeptidases and their protein inhibitors. Structure, function and biomedical properties.. Biochim Biophys Acta 2000; 1477: 284-98.
27 Jensen AF, Bukrinsky JT, Bjerrum MJ. et al. Three high-resolution crystal structures of cadmium-substituted carboxypeptidase A provide insight into the enzymatic function.. J Biol Inorg Chem 2002; 7: 490-9.
28 Abramowitz N, Schechter I, Berger A. On the size of the active site in proteases II.. Carboxypeptidase A. Biochem Biophys Res Commun 1967; 29: 862-7.
29 Tan AK, Eaton DL. Activation and characterization of procarboxypeptidase B from human plasma.. Biochemistry 1995; 34: 5811-6.
30 Myles T, Nishimura T, Yun TH. et al. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation.. J Biol Chem 2003; 278: 51059-67.
31 Wang W, Hendriks D, Scharpé S. Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen.. J Biol Chem 1994; 269: 15937-44.
32 Reverter D, Vendrell J, Canals F. et al. A carboxypeptidase inhibitor from the medical leech Hirudo medicinalis.. J Biol Chem 1998; 273: 32927-33.
33 Ryan CA, Hass GM, Kuhn RW. Purification and properties of a carboxypeptidase inhibitor from potatoes.. J Biol Chem 1974; 249: 5495-9.
34 Hass GM, Hermodson MA. Amino sequence of a carboxypeptidase inhibitor from tomato fruits.. Biochemistry 1981; 20: 2256-60.
35 Normant E, Martres MP, Schwartz JC. et al. Purification, cDNA cloning, functional expression, and characterization of a 26-kDa endogenous mammalian carboxypeptidase inhibitor.. Proc Natl Acad Sci USA 1988; 92: 12225-9.
36 Lazoura E, Campbell W, Yamaguchi Y. et al. Rational structure-based design of a novel carboxypeptidase R inhibitor.. Chem Biol 2002; 9: 1129-39.
37 Barrow JC, Nantermet PG, Stauffer SR. et al. Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics.. J Med Chem 2003; 46: 5294-7.
38 Allerton CMN, Blagg J, Bunnage ME. et al. Substituted imidazoles as TAFIa inhibitors.. Patent WO 02/14285.
39 Polla M, Tottie L, Bauer M. et al. Design and synthesis of the first potent, orally active, inhibitors of carboxypeptidase U (TAFIa).. Bioorg Med Chem 2004; 12: 1151-75.
40 Suzuki K, Muto Y, Fushihara K. et al. Enhancement of fibrinolysis by EF6265, a specific inhibitor of plasma carboxypeptidase B.. J Pharmacol Exp Ther 2004; 309: 607-15.
41 Walker JB, Hughes B, James I. et al. Stabilization versus inhibition of TAFIa by competitive inhibitors in vitro.. J Biol Chem 2003; 278: 8913-21.
42 Mao SS, Colussi D, Bailey CM. et al. Electrochemiluminescence assay for basic carboxypeptidases: inhibition of basic carboxypeptidases and activation of thrombin-activatable fibrinolysis inhibitor.. Anal Biochem 2003; 319: 159-70.
43 Marx P, Havik S, Marquart JA. et al. Generation and characterization of a highly stable form of activated TAFI.. J Biol Chem 2004; 279: 6620-8.
44 Hashimoto M, Yamashita T, Oiwa K. et al. Enhancement of endogenous plasminogen activator-induced thrombolysis by argatroban and APC and its control by TAFI, measured in an arterial thrombolysis model in vivo using rat mesenteric arterioles.. Thromb Haemost 2002; 87: 110-3.
45 Valnickova Z, Thogersen IB, Christensen S. et al. Activated human plasma carboxypeptidase B is retained in the blood by binding to α2-macroglobulin and pregnancy zone protein.. J Biol Chem 1996; 271: 12937-43.
46 Valnickova Z, Enghild JJ. Human procarboxypeptidase U, or thrombin-activable fibrinolysis inhibitor, is a substrate for transglutaminases. Evidence for transglutaminase- catalyzed cross-linking to fibrin.. J Biol Chem 1998; 273: 27220-4.
47 Björquist P, Andréasson A-C, Boberg B-M. et al. Immunohistochemical localisation of carboxypeptidase U in human thrombi.. Fibrinolysis & Proteolysis 2000; 14: 0-88.
48 Mutch NJ, Moore NR, Wang E. et al. Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI.. J Thromb Haemost 2003; 1: 2000-7.
49 Kawamura T, Okada N, Okada H. Elastase from activated human neutrophils activates procarboxypeptidase R.. Microbiol Immunol 2002; 46: 225-30.
50 Schatteman K, Goossens F, Scharpé S. et al. Proteolytic activation of purified human procarboxypeptidase U.. Clin Chim Acta 2000; 292: 25-40.
51 Côté HC, Bajzar L, Stevens WK. et al. Functional characterization of recombinant human meizothrombin and meizothrombin(desF1). Thrombomodulin-dependent activation of protein C and thrombin-activatable fibrinolysis inhibitor (TAFI), platelet aggregation, antithrombin-III inhibition.. J Biol Chem 1997; 272: 6194-200.
52 Boffa MB, Bell R, Stevens WK. et al. Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor.. J Biol Chem 2000; 275: 12868-78.
53 Marx PF, Hackeng TM, Dawson PE. et al. Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage.. J Biol Chem 2000; 275: 12410-5.
54 Marx PF, Dawson PE, Bouma BN. et al. Plasminmediated activation and inactivation of thrombin-activatable fibrinolysis inhibitor.. Biochemistry 2002; 41: 6688-96.
55 Leurs J, Wissing BM, Nerme V. et al. Different mechanisms contribute to the biphasic pattern of carboxypeptidase U (TAFIa) generation during in vitro clot lysis in human plasma.. Thromb Haemost 2003; 89: 264-71.
56 Wu CL, Dong NZ, da Cunha V. et al. Activated thrombin-activatable fibrinolysis inhibitor attenuates spontaneous fibrinolysis of batroxobin-induced fibrin deposition in rat lungs.. Thromb Haemost 2003; 90: 414-21.
57 Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex.. J Biol Chem 1996; 271: 16603-8.
58 Wang W, Nagashima M, Schneider M. et al. Elements of the primary structure of thrombomodulin required for efficient thrombin-activable fibrinolysis inhibitor activation.. J Biol Chem 2000; 275: 22942-7.
59 Kokame K, Zheng X, Sadler JE. Activation of thrombin-activable fibrinolysis inhibitor requires epidermal growth factor-like domain 3 of thrombomodulin and is inhibited competitively by protein C.. J Biol Chem 1998; 273: 12135-9.
60 Leung LL, Hall SW. Dissociation of thrombin’s substrate interactions using site-directed mutagenesis.. Trends Cardiovascular Med 2000; 10: 89-92.
61 Hall SW, Nagashima M, Zhao L. et al. Thrombin interacts with thrombomodulin, protein C, and thrombinactivatable fibrinolysis inhibitor via specific and distinct domains.. J Biol Chem 1999; 274: 25510-6.
62 Bell R, Stevens WK, Jia Z. et al. Fluorescence properties and functional roles of tryptophan residues 60d, 96, 148, 207, and 215 of thrombin.. J Biol Chem 2000; 275: 29513-20.
63 Glaser CB, Morser J, Clarke JH. et al. Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation.. J Clin Invest 1992; 90: 2565-73.
64 Esmon CT. Protein C, protein S and thrombomodulin.. Colman RW, Hirsh JH, Marder VJ, Clowes AW, George JN. Hemostasis and thrombosis, basic principles and clinical practice.. London: Lippincott Williams & Wilkins; 2001: 336-53.
65 Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent.. Blood 1996; 88: 2093-100.
66 Mosnier LO, Meijers JC, Bouma BN. Regulation of fibrinolysis in plasma by TAFI and protein C is dependent on the concentration of thrombomodulin.. Thromb Haemost 2001; 85: 5-11.
67 Mao SS, Cooper CM, Wood T. et al. Characterization of plasmin-mediated activation of plasma procarboxypeptidase B. Modulation by glycosaminoglycans.. J Biol Chem 1999; 274: 35046-52.
68 Wang W, Boffa MB, Bajzar L. et al. A study of the mechanism of inhibition of fibrinolysis by activated thrombin-activable fibrinolysis inhibitor.. J Biol Chem 1998; 273: 27176-81.
69 Esmon CT. The role of protein C and thrombomodulin in the regulation of blood coagulation.. J Biol Chem 1989; 264: 4743-6.
70 Weitz JI, Leslie B, Hudoba M. Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors.. Circulation 1998; 97: 544-52.
71 Mutch NJ, Robbie LA, Booth NA. Human thrombi contain an abundance of active thrombin.. Thromb Haemost 2001; 86: 1028-34.
72 Nesheim M. Thrombin and fibrinolysis.. Chest 2003; 124: 33S-39S.
73 Marx PF, Bouma BN, Meijers JC. Role of zinc ions in activation and inactivation of thrombin- activatable fibrinolysis inhibitor.. Biochemistry 2002; 41: 1211-6.
74 Schatteman K, Goossens F, Scharpé S. et al. Assay of procarboxypeptidase U, a novel determinant of the fibrinolytic cascade, in human plasma.. Clin Chem 1999; 45: 807-13.
75 Schneider M, Boffa M, Stewart R. 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.. J Biol Chem 2002; 277: 1021-30.
76 Boffa MB, Reid TS, Joo E. et al. Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B).. Biochemistry 1999; 38: 6547-58.
77 Tsai SP, Drayna D. The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome.
78 Boffa MB, Hamill JD, Bastajian N. et al. A role for CCAAT/enhancer-binding protein in hepatic expression of thrombin-activable fibrinolysis inhibitor.. J Biol Chem 2002; 277: 25329-36.
79 Boffa MB, Hamill JD, Maret D. et al. Acute phase mediators modulate thrombin-activable fibrinolysis inhibitor (TAFI) gene expression in HepG2 cells.. J Biol Chem 2003; 278: 9250-7.
80 Franco RF, Fagundes MG, Meijers JC. et al. Identification of polymorphisms in the 5’-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.. Haematologica 2001; 86: 510-7.
81 Maret D, Boffa M, Brien D. et al. Role of mRNA transcript stability in modulation of expression of the gene encoding thrombin activable fibrinolysis inhibitor.. J Thomb Haemost 2004; 2: 1969-79.
82 Volpi R, Zito F, Di Castelnuovo A, Donati BM, Lacoviello L. Genetic-environmental interactions in relation to atherothrombosis.. Arnout J, de Gaetano G, Hoylaerts M, Peerlinck K, VanGeet C, Verhaeghe R. Thrombosis: fundamental and clinical aspects.. Leuven: Leuven University Press; 2003: 328-45.
83 Brouwers GJ, Vos HL, Leebeek FW. 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.. Blood 2001; 98: 1992-3.
84 Henry M, Aubert H, Morange PE. 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.. Blood 2001; 97: 2053-8.
85 Zhao L, Morser J, Bajzar L. et al. Identification and characterization of two thrombin-activatable fibrinolysis inhibitor isoforms.. Thromb Haemost 1998; 80: 949-55.
86 Gils A, Alessi MC, Brouwers E. et al. Development of a genotype 325-specific proCPU/TAFI ELISA.. Arterioscler Thromb Vasc Biol 2003; 23: 1122-7.
87 Guimarães A, vanTilburg N, Vos H. et al. Association between thrombin activatable fibrinolysis inhibitor genotype and levels in plasma: comparison of different assays.. BJH 2004; 124: 659-65.
88 Mosnier LO, Buijtenhuijs P, Marx PF. et al. Identification of thrombin activatable fibrinolysis inhibitor (TAFI) in human platelets.. Blood 2003; 101: 4844-6.
89 Vanhoof G, Schatteman K, Goossens F. et al. Procarboxypeptidase U is expressed in human liver.. Fibrinolysis & Proteolysis 1997; (Suppl. 02) 3: 41.
90 Fujimoto H, Gabazza EC, Hataji O. et al. Thrombinactivatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease.. Am J Respir Crit Care Med 2003; 167: 1687-94.
91 Aubert H, Frère C, Aillaud MF. et al. Weak and nonindependent association between plasma TAFI antigen levels and the insulin resistance syndrome.. J Thromb Haemost 2003; 1: 791-7.
92 Hori Y, Gabazza EC, Yano Y. et al. Insulin resistance is associated with increased circulating level of thrombin- activatable fibrinolysis inhibitor in type 2 diabetic patients.. J Clin Endocrinol Metab 2002; 87: 660-5.
93 Falk K, Björquist P, Falk P. et al. Antifibrinolytic proCPU is present in the peritoneal cavity during surgery.. Scand J Clin Lab Invest 2003; 63: 287-96.
94 Mosnier LO, von dem Borne PA, Meijers JC. et al. Plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation.. Thromb Haemost 1998; 80: 829-35.
95 Guo X, Morioka A, Kaneko Y. et al. Arginine carboxypeptidase (CPR) in human plasma determined with sandwich ELISA.. Microbiol Immunol 1999; 43: 691-8.
96 Strömqvist M, Schatteman K, Leurs J. et al. Immunological assay for the determination of procarboxypeptidase U antigen levels in human plasma.. Thromb Haemost 2001; 85: 12-17.
97 Schatteman K, Goossens F, Leurs J. et al. Fast homogeneous assay for plasma procarboxypeptidase U.. Clin Chem Lab Med 2001; 39: 806-10.
98 Watanabe M, Ishikawa Y, Campbell W. et al. Measurement of arginine carboxypeptidase-generating activity of adult plasma.. Microbiol Immunol 1998; 42: 393-7.
99 Mosnier LO, Elisen MG, Bouma BN. et al. Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation.. Thromb Haemost 2001; 86: 1057-64.
100 Neill E, Stewart R, Schneider M. et al. A functional assay for measuring activated thrombin-activatable fibrinolysis inhibitor in plasma.. Anal Biochem 2004; 330: 332-41.
101 Reijerkerk A, Voest EE, Gebbink MF. No grip, no growth: the conceptual basis of excessive proteolysis in the treatment of cancer.. Eur J Cancer 2000; 36: 1695-705.
102 Plow EF, Allampallam K, Redlitz A. The plasma carboxypeptidases and the regulation of the plasminogen system.. Trends Cardiovasc Med 1997; 7: 71-5.
103 Li WY, Chong SSN, Huang EY. et al. Plasminogen activator/plasmin system: A major player in wound healing?. Wound Rep Reg 2003; 11: 239-47.
104 Lijnen HR. Plasmin and matrix metalloproteinases in arterial restenosis and atherosclerosis.. Arnout J, deGaetano G, Hoylaerts M, Peerlinck K, VanGeet C, Verhaeghe R. Thrombosis: fundamental and clinical aspects.. Leuven: Leuven University Press; 2003: 266-79.
105 Colman RW, Clowes AW, George JN, Hirsh JH, Marder VJ. Overview of Haemostasis.. Colman RW, Hirsh JH, Marder VJ, Clowes AW, George JN. Hemostasis and Thrombosis: Basic principles and clinical practice.. New York: Lippincott Williams & Wilkins; 2001: 3-16.
106 Medved L, Nieuwenhuizen W. Molecular mechanisms of inititation of fibrinolysis by fibrin.. Thromb Haemost 2003; 89: 409-19.
107 Sakharov DV, Plow EF, Rijken DC. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B.. J Biol Chem 1997; 272: 14477-82.
108 Suenson E, Lutzen O, Thorsen S. Initial plasmindegradation of fibrin as the basis of a positive feedback mechanism in fibrinolysis.. Eur J Biochem 1984; 140: 513-22.
109 Fleury V, Angles-Cano E. Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines.. Biochemistry 1991; 30: 7630-8.
110 Pannell R, Black J, Gurewich V. Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained.. J Clin Invest 1988; 81: 853-9.
111 Hoylaerts M, Rijken DC, Lijnen HR. Kinetics of the activation of plasminogen by human tissue plasminogen activator.. J Biol Chem 1982; 257: 2912-9.
112 Schneider M, Nesheim M. A study of the protection of plasmin from antiplasmin inhibition within an intact fibrin clot during the course of clot lysis.. J Biol Chem 2004; 279: 13333-9.
113 Schneider M, Brufatto N, Neill E. et al. Activated thrombin-activatable fibrinolysis inhibitor reduces the ability of high-molecular weight fibrin degradation products to protect plasmin from antiplasmin.. J Biol Chem 2004; 279: 13340-5.
114 Leurs J, Nerme V, Sim Y. et al. Carboxypeptidase U (TAFIa) prevents lysis from proceeding into the propagation phase through a threshold-dependent mechanism.. J Thromb Haemost 2004; 2: 416-23.
115 Walker J, Bajzar L. The intrinsic threshold of the fibrinolytic system is modulated by basic carboxypeptidases, but the magnitude of the antifibrinolytic effect of activated thrombin-activatable fibrinolysis inhibitor is masked by its instability.. J Biol Chem 2004; 279: 27896-904.
116 Broze GJ, Higuchi DA. Coagulation-dependent inhibition of fibrinolysis: role of carboxypeptidase-U and the premature lysis of clots from hemophilic plasma.. Blood 1996; 88: 3815-23.
117 Schatteman K, Goossens F, Scharpé S. et al. Activation of plasma procarboxypeptidase U in different mammalian species points to a conserved pathway of inhibition of fibrinolysis.. Thromb Haemost 1999; 82: 1718-21.
118 Redlitz A, Nicolini FA, Malycky JL. et al. Inducible carboxypeptidase activity. A role in clot lysis in vivo.. Circulation 1996; 93: 1328-30.
119 Von dem Borne PA, Bajzar L, Meijers JC. et al. Thrombin-mediated activation of factor XI results in a thrombin- activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis.. J Clin Invest 1997; 99: 2323-7.
120 Hosaka Y, Takahashi Y, Ishii H. Thrombomodulin in human plasma contributes to inhibit fibrinolysis through acceleration of thrombin-dependent activation of plasma procarboxypeptidase B.. Thromb Haemost 1998; 79: 371-7.
121 Schneider M, Nesheim M. Reversible inhibitors of TAFIa can both promote and inhibit fibrinolysis.. J Thromb Haemost 2003; 1: 147-54.
122 Mann KG. Thrombin formation.. Chest 2003; 124: 4S-10S.
123 Hemker HC, Béguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential.. Thromb Haemost 1995; 74: 134-8.
124 Mosnier LO, Lisman T, van den Berg HM. et al. The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration.. Thromb Haemost 2001; 86: 1065-9.
125 Von dem Borne PA, Meijers JC, Bouma BN. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis.. Blood 1995; 86: 3035-42.
126 Antovic JP, Antovic A. Does recombinant factor Vlla, apart from overall hemostasis, regulate TAFI dependent fibrinolysis? In vitro analysis using overall hemostasis potential (OHP) assay.. Thromb Haemost 2003; 90: 620-7.
127 Lisman T, Mosnier LO, Lambert T. et al. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe hemophilia A.. Blood 2002; 99: 175-9.
128 Bajzar L, Kalafatis M, Simioni P. et al. An antifibrinolytic mechanism describing the prothrombotic effect associated with factor V Leiden.. J Biol Chem 1996; 271: 22949-52.
129 Colucci M, Binetti BM, Tripodi A. et al. Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFImediated mechanism.. Blood 2004; 103: 2157-61.
130 Mosnier LO, Meijers JC, Bouma BN. The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis.. Thromb Haemost 2001; 86: 1040-6.
131 Kato T, Akatsu H, Sato T. et al. Molecular cloning and partial characterization of rat procarboxypeptidase R and carboxypeptidase N.. Microbiol Immunol 2000; 44: 719-28.
132 Marx PF, Wagenaar GT, Reijerkerk A. et al. Characterization of mouse thrombin-activatable fibrinolysis inhibitor.. Thromb Haemost 2000; 83: 297-303.
133 Sato T, Miwa T, Akatsu H. et al. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not.. J Immunol 2000; 165: 1053-8.
134 Klement P, Liao P, Bajzar L. A novel approach to arterial thrombolysis.. Blood 1999; 94: 2735-43.
135 Komura H, Shimomura Y, Yumoto M. et al. Heat stability of carboxypeptidase R of experimental animals.. Microbiol Immunol 2002; 46: 217-23.
136 Mattsson C, Björkman JA, Abrahamsson T. et al. Local proCPU (TAFI) activation during thrombolytic treatment in a dog model of coronary artery thrombosis can be inhibited with a direct, small molecule thrombin inhibitor (melagatran).. Thromb Haemost 2002; 87: 557-62.
137 Nagashima M, Werner M, Wang M. et al. An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model.. Thromb Res 2000; 98: 333-42.
138 Minnema MC, Friederich PW, Levi M. 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.. J Clin Invest 1998; 101: 10-14.
139 Refino CJ, Deguzman L, Schmitt D. et al. Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and hemostasis.. Fibrinolysis & Proteolysis 2000; 14: 305-14.
140 Muto Y, Suzuki K, Sato E, Ishii H. Carboxypeptidase B inhibitors reduce tissue factor-induced renal microthrombi in rats.. Eur J Pharmacol 2003; 461: 181-9.
141 Nerme V, Åkerblom B, Abrahamsson T. The combined inhibition of carboxypeptidase U and thrombin increases synergistically the rate of fibrinolysis in a rat DIC model.. Blood 2000; 96: 47a.
142 Juhan-Vague I, Renucci JF, Grimaux M. et al. Thrombin-activatable fibrinolysis inhibitor antigen levels and cardiovascular risk factors.. Arterioscler Thromb Vasc Biol 2000; 20: 2156-61.
143 Montaner J, Ribó M, Monasterio J. et al. Thrombin- activable fibrinolysis inhibitor levels in the acute phase of ischemic stroke.. Stroke 2003; 34: 1038-40.
144 Santamaría A, Oliver A, Borrell M. et al. Risk of ischemic stroke associated with functional thrombinactivatable fibrinolysis inhibitor plasma levels.. Stroke 2003; 34: 2387-91.
145 Lau HK, Segev A, Hegele RA. et al. Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis.. Thromb Haemost 2003; 90: 1187-91.
146 Silveira A, Schatteman K, Goossens F. et al. Plasma procarboxypeptidase U in men with symptomatic coronary artery disease.. Thromb Haemost 2000; 84: 364-8.
147 Morange PE, Juhan-Vague I, Scarabin PY. et al. Association between TAFI antigen and Ala 147Thr polymorphism of the TAFI gene and the angina pectoris incidence – The PRIME Study.. Thromb Haemost 2003; 89: 554-60.
148 Juhan-Vague I, Morange PE, Aubert H. et al. Plasma thrombin-activatable fibrinolysis inhibitor antigen concentration and genotype in relation to myocardial infarction in the north and south of Europe.. Arterioscler Thromb Vasc Biol 2002; 22: 867-73.
149 Juhan-Vague I, Morange PE. Very high TAFI antigen levels are associated with a lower risk of hard coronary events: the PRIME Study.. J Thromb Haemost 2003; 1: 2243-4.
150 Libourel E, Bank I, Meinardi J. et al. Co-segregation of thrombophilic disorders in factor V Leiden carriers; the contributions of factor VIII, factor XI, thrombin activatable fibrinolysis inhibitor and lipoprotein(a) to the absolute risk of venous thromboembolism.. Haematologica 2002; 87: 1068-73.
151 Schroeder V, Kucher N, Kohler HP. Role of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with acute pulmonary embolism.. J Thromb Haemost 2003; 1: 492-3.
152 van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis.. Blood 2000; 95: 2855-9.
153 Brouwers GJ, Leebeek F, Tanck M. et al. Association between thrombin-activatable fibrinolysis inhibitor (TAFI) and clinical outcome in patients with unstable angina pectoris.. Thromb Haemost 2003; 90: 92-100.
154 Ribo M, Montaner J, Molina C. et al. Admission fibrinolytic profile predicts clot lysis resistance in stroke patients treated with tissue plasminogen activator.. Thromb Haemost 2004; 91: 1146-51.
155 Salomon O, Steinberg DM, Dardik R. et al. Inherited factor XI deficiency confers no protection against acute myocardial infarction.. J Thromb Haemost 2003; 1: 658-61.
156 Schroeder V, Chatterjee T, Mehta H. et al. Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels in patients with coronary artery disease investigated by angiography.. Thromb Haemost 2002; 88: 1020-5.
157 Zorio E, Castelló R, Falcó C. et al. Thrombin-activatable fibrinolysis inhibitor in young patients with myocardial infarction and its relationship with the fibrinolytic function and the protein C system.. Br J Haematol 2003; 122: 958-65.
158 Colucci M, Binetti BM, Branca MG. et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis.. Hepatology 2003; 38: 230-7.
159 Lisman T, Leebeek F, Mosnier L. et al. Thrombinactivatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis.. Gastroenterology 2001; 121: 131-9.
160 vanGorp E, Minnema M, Suharti C. et al. Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever.. Br J Haematol 2001; 113: 94-9.
161 van Thiel DH, George M, Fareed J. Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease.. Thromb Haemost 2001; 85: 667-70.
162 Watanabe R, Wada H, Watanabe Y. et al. Activity and antigen levels of thrombin-activatable fibrinolysis inhibitor in plasma of patients with disseminated intravascular coagulation.. Thromb Res 2001; 104: 1-6.
163 Antovic J, Schulman S, Eelde A. et al. Total thrombin- activatable fibrinolysis inhibitor (TAFI) antigen and pro-TAFI in patients with haemophilia A.. Haemophilia 2001; 7: 557-60.
164 Meijers J, Oudijk EJ, Mosnier L. et al. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia.. Br J Haematol 2000; 108: 518-23.
165 Brzosko S, Hryszko T, Lebkowska U. et al. Plasma tissue-type plasminogen activator, fibrinogen, and time on dialysis prior to transplantation are related to carotid intima media thickness in renal transplant recipients.. Transplantation Proceedings 2003; 35: 2931-4.
166 Hryszko T, Malyszko J, Malyszko JS. et al. Patients on peritoneal dialysis but not on hemodialysis have elevated concentration and activity of thrombin-activatable fibrinolysis inhibitor.. Thromb Res 2001; 104: 233-8.
167 Hryszko T, Malyszko J, Malyszko JS. et al. A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients.. Nephrol Dial Transplant 2001; 16: 1692-6.
168 Malyszko J, Malyszko JS, Hryszko T. et al. Thrombin- activatable fibrinolysis inhibitor in kidney transplant recipient with dyslipidemia.. Transplantation Proceedings 2003; 35: 2219-21.
169 Malyszko J, Malyszko JS, Mysliwiec M. Markers of endothelial cell injury and thrombin activatable fibrinolysis inhibitor in nephrotic syndrome.. Blood Coagul Fibrinol 2002; 13: 615-21.
170 Malyszko J, Suchowierska E, Malyszko JS. et al. Some aspects of haemostasis in CAPD patients treated with erythropoietin.. Kidney Blood Press Res 2002; 25: 240-4.
171 Malyszko J, Malyszko JS, Hryszko T. et al. Simvastatin affects TAFI and thrombomodulin in CAPD patients.. Thromb Haemost 2001; 86: 930-1.
172 Malyszko J, Malyszko JS, Hryszko T. et al. Some aspects of haemostasis in kidney transplant recipients maintained on cyclosporine, azathioprine, and predni-sone in comparison to patients treated with cyclosporine and prednisone.. Transplantation Proceedings 2003; 35: 2940-2.
173 Antovic JP, Yngen M, Östenson CG. et al. Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.. Blood Coagul Fibrinol 2003; 14: 551-6.
174 Bruni F, Pasqui A, Pastorelli M. et al. Effect of atorvastatin on different fibrinolysis mechanisms in hypercholesterolemic subjects.. Int J Cardiol 2004; 95: 269-74.
175 Malysko J, Malysko J, Hryszko T. et al. Simvastatin affects TAFI and thrombomodulin in CAPD patients.. Thromb Haemost 2001; 86: 930-1.
176 Schatteman K, VanGaal L, Goossens F. et al. Increased procarboxypeptidase U levels in type II diabetes may reflect decreased firbinolytic rate.. Fibrinolysis & Proteolysis 2000; 14: 69.
177 Yano Y, Kitagawa N, Gabazza EC. et al. Increased plasma thrombin-activatable fibrinolysis inhibitor levels in normotensive type 2 diabetic patients with microalbuminuria.. J Clin Endocrinol Metab 2003; 88: 736-41.
178 Alacacioğlu I, Özcan M, Alacaclølu A. et al. Plasma levels of thrombin activatable fibrinolysis inhibitor in normal and preeclamptic pregnant women.. Thromb Res 2004; 114: 155-59.
179 Antovic JP, Rafik HR, Antovic A. et al. Does thrombin activatable fibrinolysis inhibitor (TAFI) contribute to impairment of fibrinolysis in patients with preeclampsia and/or intrauterine fetal growth retardation?. Thromb Haemost 2002; 88: 644-7.
180 Bladbjerg EM, Madsen JS, Kristensen SR. et al. Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausalwomen: a randomized controlled study.. J Thromb Haemost 2003; 1: 1208-14.
181 Kemmeren JM, Algra A, Meijers JC. et al. Effect of second- and third- generation oral contraceptives on fibrinolysis in the absence and presence of the factor V Leiden mutation.. Blood Coagul Fibrinolysis 2002; 13: 373-81.
182 Meijers J, Middeldorp S, Tekelenburg W. et al. Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives.. Thromb Haemost 2000; 84: 9-14.
183 Post MS, Hendriks DF, Van Der Mooren MJ. et al. Oral oestradiol/trimegestone replacement reduces procarboxypeptidase U (TAFI): a randomized, placebocontrolled, 12-week study in early postmenopausal women.. J Int Med 2002; 251: 245-51.
184 Vogelvang T, Leurs J, van der Mooren MJ. et al. Raloxifene reduces procarboxypeptidase U, an antifibrinolytic marker. A 2-year randomised, placebo-controlled study in healthy early postmenopausal women.. Menopause 2004; 11: 110-15.
185 Haijar KA, Krishnan S. Annexin II: a mediator of plasmin/plasminogen activator system.. TCM 1999; 9: 128-38.
186 Fogg DK, Bridges DE, Cheung KKT. et al. The p11 subunit of annexin II heterotetramer is regulated by basic carboxypeptidase.. J Biol Chem 2002; 41: 4953-61.
187 Skidgel RA. Structure and function of mammalian zinc carboxypeptidases.. Hooper NM. Zinc metalloproteases in health and disease.. London: Taylor and Francis Ltd; 1996: 241-83.
188 Matthews K, Mueller-Ortiz SL, Wetsel RA. Carboxypeptidase N: a pleiotropic regulator of inflammation.. Mol Immunol 2004; 40: 785-93.
189 Bouma B, Marx P, Mosnier L. et al. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U).. Thromb Res 2001; 101: 329-54.
190 Skidgel RA, Davis RM, Tan F. Human carboxypeptidase M. Purification and characterization of a membrane-bound carboxypeptidase that cleaves peptide hormones.. J Biol Chem 1989; 264: 2236-41.
191 Cyr M, Lepage Y, Blais C. et al. Adam A bradykinin and des-arg9-bradykinin metabolic pathways and kinetics of activation of human plasma.. Am J Physiol Heart Circ Physiol 2001; 281: H275-H283.
192 Nagashima M, Yin ZF, Zhao L. et al. Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life.. J Clin Invest 2002; 109: 101-10.
193 Asia S, Sato T, Tada T. et al. Absence of procarboxypeptidase R induces complement-mediated lethal inflammation in lipopolysaccharide-primed mice.. J Immunol 2004; 173: 4469-74.
194 Campbell W, Okada N, Okada H. Carboxypeptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis.. Immunol Rev 2001; 180: 162-67.
195 Campbell WD, Lazoura E, Okada N. et al. Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N.. Microbiol Immunol 2002; 46: 131-34.
196 Swaisgood CM, Schmitt D, Eaton DL. et al. In vivo regulation of the plasminogen system by plasma carboxypeptidase B.. J Clin Invest 2002; 110: 1275-82.
197 Velde E, Wagenaar G, Reijerkerk A. et al. Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor.. J Thromb Haemost 2003; 1: 2087-96.
198 Boffa MB. TAFI and wound healing: closing a knowledge gap.. J Thromb Haemost 2003; 1: 2075-7.