Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis

Summary

The fibrinolytic system is closely related to several processes that are involved in restenosis. We previously showed that low PAI-1 plasma levels predicted restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been described. The aims of this study were to evaluate the relationship between pre-procedural plasma levels of TAFI and late angiographic restenosis and the interaction between TAFI and PAI-1. We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty or stenting of de novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured in plasma samples drawn before the procedure. Follow-up coronary angiography was performed in 92% of patients. There was a significant correlation between pre-procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p = 0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural TAFI levels were significantly higher in patients with restenosis (108 ± 33% versus 94±30%, p = 0.011). Restenosis rates for patients in the upper tertile of TAFI levels were 2-fold higher than for those in the lowest tertile (45% versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels identified patients at the highest risk of restenosis (53%) compared to 14% in patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre-procedural plasma TAFI antigen levels identify patients at increased risk for restenosis after PCI.

Keywords

TAFI - PAI-1 - restenosis - fibrinolysis

^* Both authors contributed equally to this work

• References

• 1 Schwartz RS, Murphy JG, Edwards WD. et al. Restenosis after balloon angioplasty: a practical proliferative model in porcine coronary arteries. Circulation 1990; 82: 2190-200.
• 2 Strauss BH, Lau HK, Bowman KA. et al. Plasma urokinase antigen and plasminogen activator inhibitor-1 antigen levels predict angiographic coronary restenosis. Circulation 1999; 100: 1616-22.
• 3 Vassalli JD. The urokinase receptor. Fibrinolysis 1994; 8 (01) suppl 172-81.
• 4 Hendriks D, Scharpe S, van Sande M. et al. Characterization of a carboxypeptidase in human serum distinct from carboxypeptidase N. J Clin Chem Clin Biochem 1989; 27: 277-85.
• 5 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.
• 6 Bajzar L, Morser J, Nesheim M. Purification of and characterization of TAFI, a thrombinactivatable fibrinolysis inhibitor. J Biol Chem 1995; 270: 14477-84.
• 7 Bajzar L. Thrombin activatable fibrinolysis inhibitor and an antifibrinolytic pathway. Arterioscler Thromb Vasc Biol 2000; 20: 2511-8.
• 8 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.
• 9 Nesheim M, Wang W, Boffa M. et al. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 1997; 78: 386-91.
• 10 Wang W, Boffa PB, Bajzar L. et al. A study of the mechanism of inhibition of fibrinolysis by activated thrombin-activatable fibrinolysis inhibitor. J Biol Chem 1998; 273: 27176-81.
• 11 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.
• 12 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.
• 13 Miner SE, Hegele RA, Sparkes J. et al. Homocysteine, lipoprotein(a), and restenosis after percutaneous transluminal coronary angioplasty: a prospective study. Am Heart J 2000; 140: 272-8.
• 14 Foley DP, Escaned J, Strauss BH. et al. Quantitative coronary angiography (QCA) in interventional cardiology: clinical application of QCA measurements. Prog Cardiovasc Dis 1994; 36: 363-84.
• 15 Juhan-Vague I, Renucci JF, Grimaux M. et al. TAFI antigen levels and cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2000; 20: 2156-61.
• 16 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.
• 17 Jang Y, Guzman LA, Lincoff M. et al. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. Circulation 1995; 92: 3041-50.
• 18 Oltrona A, Speidel CM, Recchia D. et al. Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs. Circulation 1997; 96: 646-52.
• 19 Sakharov DV, Plow EF, Rijken DC. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B. J Biol Chem 1997; 272: 14447-82.
• 20 van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood 2000; 95: 2855-9.
• 21 Silveira A, Schatteman K, Goossens F. et al. Plasma procardoxypeptidase U in men with symptomatic coronary artery disease. Thromb Haemost 2000; 84: 364-8.
• 22 Morange PE, Juhan-Vague I, Scarabin PY. et al. Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence. Thromb Haemost 2003; 89: 554-60.
• 23 Klement P, Liao P, Bajzar L. A novel approach to arterial thrombolysis. Blood 1999; 94: 2735-43.
• 24 Tsuboi Y, Takahashi M, Ishikawa Y. et al. Elevated bradykinin and decreased carboxypeptidase R as a cause of hypotension during tryptophan column immunoabsorption therapy. Ther Apher 1998; 2: 297-9.
• 25 Monea S, Lehti K, Keski-Oja J. et al. Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism. J Cell Physiol 2002; 192: 160-70.
• 26 Rosenthal EL, Johnson TM, Allen ED. et al. Role of the plasminogen activator and matrix metalloproteinase systems in epidermal growth factor- and scatter factor-stimulated invasion of carcinoma cells. Cancer Res 1998; 58: 5221-30.
• 27 Stefansson S, Lawrence DA. The serpin PAI-1 inhibits cell migration by blocking integrin αVβ3 binding to vitronectin. Nature 1996; 383: 441-3.
• 28 Bogaty P, Poirier P, Simard S, Boyer L. et al. Biological profiles in subjects with recurrent acute coronary events compared with subjects with long-standing stable angina. Circulation 2001; 103: 3062-8.
• 29 Folsom AR, Aleksic N, Park E. et al. Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 2001; 21: 611-7.
• 30 Inoue T, Yaguchi I, Mizoguchi K. et al. Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction. Clin Cardiol 2003; 26: 153-7.