SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats

Thrombosis Journal

Keiji Hasumi¹  Naoko Nishimura¹  Ritsuko Narasaki²  Weimin Hu² 

[1] Research and Development Division, TMS Co., Ltd., 1-32-1-102 Fuchucho, Fuchu, Tokyo 183-0055, Japan;Department of Applied Biological Science, Tokyo Noko University, 3-5-8 Saiwaicho, Fuchu, Tokyo 183-8509, Japan

关键词: thromboembolism;    thrombolysis;    fibrinolysis;    plasminogen;   

Others  :  838984
DOI  :  10.1186/1477-9560-10-2

 received in 2011-08-20, accepted in 2012-01-09,  发布年份 2012

【 摘 要 】

Background

Stachybotrys microspora triprenyl phenols (SMTPs) are a novel family of small molecules that enhance both activation and fibrin-binding of plasminogen. While their effects on fibrinolysis have been characterized in vitro, little is known about their activity in vivo with respect to plasminogen activation and blood clot clearance.

Results

To select a potent SMTP congener for the evaluation of its action in vitro and in vivo, we tested several SMTP congeners with distinct structural properties for their effects on plasminogen activation. As a result, SMTP-7 (orniplabin) was found to have distinguished activity. Several lines of biochemical evidence supported the idea that SMTP-7 acted as a plasminogen modulator. SMTP-7 elevated plasma level of plasmin-α₂-antiplasmin complex, an index of plasmin formation in vivo, 1.5-fold in mice after the intravenous injections at doses of 5 and 10 mg kg^-1. In a rat pulmonary embolism model, SMTP-7 (5 mg kg^-1) enhanced the rate of clot clearance ~3-fold in the absence of exogenous plasminogen activator. Clot clearance was enhanced further by 5 mg kg^-1 of SMTP-7 in combination with single-chain urokinase-type plasminogen activator.

Conclusions

Our results show that SMTP-7 is a superior plasminogen modulator among the SMTP family compounds and suggest that the agent enhances plasmin generation in vivo, leading to clearance of thrombi in a model of pulmonary embolism.

【 授权许可】

   
2012 Hu et al; licensee BioMed Central Ltd.

【 图 表 】

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