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

Masaru Hashimoto; Tsutomu Yamashita; Kazuhiro Oiwa; Sadahiro Watanabe; John C. Giddings; Junichiro Yamamoto

doi:10.1055/s-0037-1612952

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(01): 110-113
DOI: 10.1055/s-0037-1612952

Review Article

Schattauer GmbH

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

Masaru Hashimoto

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan

,

Tsutomu Yamashita

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan

,

Kazuhiro Oiwa

²Communications Research Laboratory, Kansai Advanced Research Centre, Kobe, Japan

,

Sadahiro Watanabe

³Division of Basic Medical Science, Kobe City College of Nursing, Kobe, Japan

,

John C. Giddings

⁴Department of Haematology, University of Wales College of Medicine, Cardiff, UK

,

Junichiro Yamamoto

¹Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University and Kobe Gakuin University High Technology Research Centre, Kobe, Japan

› Author Affiliations

Abstract

Summary

Recent in vitro studies have demonstrated that thrombin inhibits fibrinolysis through thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B). We have recently shown that endogenous fibrinolysis in vivo is enhanced by activated protein C (APC) and the selective thrombin inhibitor, argatroban. The aim of the present study was to examine the role of TAFI in these fibrinolytic mechanisms in vivo using purified porcine pancreatic carboxypeptidase B (PPCPB) and a specific TAFIa inhibitor, potato tuber carboxypeptidase B inhibitor (PTCI) in a newly established arterial thrombolysis model. Non-occlusive, mural, platelet-rich thrombi were formed by helium-neon laser irradiation in rat mesenteric arterioles and thrombus size was measured by computerised image analysis. We confirmed that endogenous thrombolysis was enhanced by argatroban (2.0 mg/4 ml/kg/h) or APC (1.62 mg/2.31 ml/kg). PTCI (5.0 mg/2 ml/kg) also accelerated endogenous thrombolysis. PPCPB (3.5 mg/2 ml/kg) inhibited thrombolysis in the absence and presence of argatroban or APC. PTCI tended to further promote APC-induced thrombolysis but the differences did not reach statistical significance. The present findings were in keeping with the results of earlier studies and demonstrated that arterial, platelet-rich thrombi in vivo are degraded by naturally generated plasminogen activators. TAFI may play a significant role in the control of these mechanisms.

Keywords

Endogenous thrombolysis - fibrinolysis - thrombin - TAFI

Full Text

References

References
1 Jang IK, Gold HK, Ziskind AA, Leinbach RC, Fallon JT, Collen D. Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition. Circulation 1990; 81: 219-25.
2 Badimon L, Badimon JJ, Lassila R, Heras M, Chesebro JH, Fuster V. Thrombin regulation of platelet interaction with damaged vessel wall and isolated collagen type I at arterial flow condition in porcine model: effects of hirudins, heparin, and calcium chelation. Blood 1991; 78: 423-34.
3 Yamashita T, Yamamoto J, Sasaki Y, Matsuoka A. The antithrombotic effect of low molecular weight synthetic thrombin inhibitors, argatroban and PPACK, on He-Ne laser-induced thrombosis in rat mesenteric microvessels. Thromb Res 1993; 69: 93-100.
4 Sasaki Y, Morii S, Yamashita T, Yamamoto J. Antithrombotic effect of argatroban on the pial vessels of the rat: a study with He-Ne laser-induced thrombus formation. Haemostasis 1993; 23: 104-11.
5 Antman EM. for the TIMI 9A Investigators. Hirudin in acute myocardial infarction: safety report from the thrombolysis and thrombin inhibition in myocardial infarction (TIMI) 9A trial. Circulation 1994; 90: 1624-30.
6 GUSTO IIb investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Eng J Med 1996; 335: 775-82.
7 Bajzar L, Nesheim M. The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. J Biol Chem 1993; 268: 8608-16.
8 von dem Borne PA, Bajzar L, Meijers JCM, Nesheim ME, Bouma BN. Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. J Clin Invest 1997; 99: 2323-7.
9 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.
10 Wang W, Boffa MB, Bajzar L, Walker JB, Nesheim ME. A study of the mechanism of inhibition of fibrinolysis by activated thrombin-activable fibrinolysis inhibitor. J Biol Chem 1998; 273: 27176-81.
11 Krement P, Liao P, Bajzar L. A novel approach to arterial thrombolysis. Blood 1999; 94: 2735-43.
12 Redlitz A, Nicolini FA, Malycky JL, Topol EJ, Plow EF. Inducible carboxypeptidase activity. Circulation 1996; 93: 1328-30.
13 Nagashima M, Werner M, Wang M, Zhao L, Light DR, Pagila R, Morser J, Verhallen P. 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.
14 Minnema MC, Friederich PW, Levi M, von dem Borne PA, Mosnier LO, Meijers JCM, Biemond BJ, Hack CE, Bouma BN, ten Cate H. Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. J Clin Invest 1998; 101: 10-4.
15 Kawano M, Watanabe S, Sasaki Y, Giddings JC, Yamamoto J. Adjuvant effect of argatroban on staphylokinase induced thrombolysis of platelet rich thrombi in rat mesenteric venules in vivo. Thromb Res 1997; 86: 115-26.
16 Yamamoto J, Kawano M, Hashimoto M, Sasaki Y, Yamashita T, Taka T, Watanabe S, Giddings JC. Adjuvant effect of antibodies against von Willebrand factor, fibrinogen, and fibronectin on staphylokinase-induced thrombolysis as measured using mural thrombi formed in rat mesenteric venules. Thromb Res 2000; 97: 327-33.
17 Hashimoto M, Yamashita T, Oiwa K, Watanabe S, Ohta Y, Yamamoto J. Inhibition of arterial thrombolysis by thrombin-activatable fibrinolysis inhibitor (TAFI) as measured in a thrombolysis model using a rat mesenteric arteriole. Fibrinolysis and proteolysis 2000; 14 suppl, 71 (Abstract).
18 Hashimoto M, Watanabe S, Oiwa K, Ohta Y, Kishi T, Okamtoto T, Giddings JC, Yamamoto J. Enhanced thrombolysis induced by argatroban or activated protein C in the presence or absence of staphylokinase, measured in an in vivo animal model using mesenteric arterioles. Haemostasis 2001; 31: 80-9.
19 Kovacs IB, Tigyi-Sebes A, Trombitas K, Gorog P. Evans blue: an ideal energy-absorbing material to produce intravascular microinjury by the He-Ne gas laser. Microvasc Res 1975; 10: 107-24.
20 Yamamoto J, Iizumi H, Hirota R, Shimonaka K, Nagamatsu Y, Horie N, Morita S. Effect of physical training on thrombotic tendency in rats: decrease in thrombotic tendency measured by the He-Ne laser-induced thrombus formation method. Haemostasis 1989; 19: 260-5.
21 Haskel EJ, Prager NA, Sobel BE, Abendschein DR. Relative efficacy of anti thrombin compared with antiplatelet agents in accelerating coronary thrombolysis and preventing early reocclusion. Circulation 1991; 83: 1048-56.
22 Klement P, Borm A, Hirsh J, Maraganore J, Wilson G, Weitz J. The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model. Thromb Haemost 1992; 68: 64-70.
23 Meyer BJ, Badimon JJ, Chesebro JH, Fallon JT, Fuster V, Badimon L. Dissolution of mural thrombus by specific thrombin inhibition with r-hirudin. Circulation 1998; 97: 681-5.
24 Yamamoto J, Oyama T, Ishii I, Okita N, Sasaki Y, Yamashita T, Matsuoka A, Muraki T, Giddings JC, Watanabe S, Seki J. The differential involvement of von Willebrand factor, fibrinogen and fibronectin in acute experimental thrombosis in rat cerebral and mesenteric microvessels. Jpn J Physiol 1997; 47: 431-41.
25 Povlishock JT, Rosenblum WI. Injury of brain microvessels with a helium-neon laser and Evans blue can elicit local platelet aggregation without endothelial denudation. Arch Pathol Lab Med 1987; 111: 415-21.
26 Iwamoto M. Plasminogen-plasmin system. IX. Specific binding of tranexamic acid to plasmin. Thromb Diath Haemorrh 1975; 33: 573-85.
27 Pascual R, Burgos FJ, Salva M, Soriano F, Mendez E, Aviles FX. Purification and properties of five different forms of human procarboxypeptidases. Eur J Biochem 1989; 179: 609-16.
28 Eaton DL, Malloy BE, Tsai SP, Henzel W, Drayna D. Isolation, molecular cloning and partial characterization of a novel carboxypeptidase B from human plasma. J Biol Chem 1991; 266: 21833-8.
29 Gailani D, Broze Jr GJ. Factor XI activation in a revised model of blood coagulation. Science 1991; 253: 909-12.
30 Oliver JA, Monroe DM, Roberts HR, Hoffman M. Thrombin activates factor XI on activated platelets in the absence of factor XII. Arterioscler Thromb Vasc Biol 1999; 19: 170-7.
31 Sakata Y, Loskutoff DJ, Gladson CL, Hekman CM, Griffin JH. Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor. Blood 1986; 68: 1218-23.
32 de Fouw NJ, Haverkate F, Bertina RM, Koopman J, van Wijngaarden A, van Hinsbergh VWM. Cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vivo. Blood 1986; 67: 1189-92.
33 Mao SS, Cooper CM, Wood T, Shafer JA, Gardell SJ. Characterization of plasmin-mediated activation of plasma carboxypeptidase B. J Biol Chem 1999; 274: 35046-52.