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Thromb Haemost 2003; 89(05): 820-825
DOI: 10.1055/s-0037-1613467
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Suppression of argatroban-induced endogenous thrombolysis by PKSI-527, and antibodies to TPA and UPA, evaluated in a rat arterial thrombolysis model

Masaru Hashimoto
1   Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe
2   High Technology Research Centre, Kobe Gakuin University, Kobe
,
Kazuhiro Oiwa
3   Communications Research Laboratory, Kansai Advanced Research Centre, Kobe
,
Osamu Matsuo
4   Second Department of Physiology, Kinki University School of Medicine, Osaka
,
Shigeru Ueshima
4   Second Department of Physiology, Kinki University School of Medicine, Osaka
,
Kiyotaka Okada
4   Second Department of Physiology, Kinki University School of Medicine, Osaka
,
Yoshio Okada
2   High Technology Research Centre, Kobe Gakuin University, Kobe
6   Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan
,
Shosuke Okamoto
5   Kobe Research Projects on Thrombosis and Haemostasis, Kobe,
,
John C. Giddings
7   Department of Haematology, University of Wales College of Medicine, Cardiff, UK
,
Junichiro Yamamoto
1   Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe
2   High Technology Research Centre, Kobe Gakuin University, Kobe
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Publikationsverlauf

Received 25. September 2002

Accepted after revision 15. Februar 2003

Publikationsdatum:
09. Dezember 2017 (online)

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Summary

We have previously confirmed, using a rat mesenteric arteriole thrombolysis model, that thrombin inhibition induces endogenous thrombolysis in vivo. In addition, we have shown that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the down regulation of endogenous thrombolysis. However, the mechanism of endogenous thrombolysis or spontaneous plasmin generation in vivo remains unclear.

It has been shown in an in vitro system that plasma kallikrein activates pro-urokinase (pro uPA) and/or plasminogen, resulting in plasmin generation. These findings suggest that spontaneous fibrinolysis might be mediated by tPA and plasma kallikrein-dependent uPA. The aim of the present study was to examine whether these mechanisms play a dominant role in endogenous thrombolysis in vivo, using our rat mesenteric arterial thrombolysis model.

Argatroban infusion enhanced endogenous thrombolysis. PKSI-527, anti uPA and anti tPA IgGs suppressed argatroban-induced thrombolysis. Also, the antibody IgG preparations suppressed endogenous thrombolysis in the absence of argatroban. In the presence of PKSI-527, anti tPA IgG was more effective than anti uPA IgG in suppressing argatroban-induced thrombolysis. The results suggested that both tPA and plasma kallikrein-mediated uPA activation and tPA release contribute to endogenous fibrinolytic or thrombolytic mechanisms.

Keywords

Endogenous thrombolysis - plasma kallikrein - plasminogen activator - TAFI - animal model
 

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