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

Thrombosis Journal

Original Basic Research

Ritsuko Narasaki¹  Weimin Hu¹  Keiji Hasumi²  Naoko Nishimura³ 

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

关键词: plasminogen;    fibrinolysis;    thrombolysis;    thromboembolism;   

DOI  :  10.1186/1477-9560-10-2

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

来源: Springer

【 摘 要 】

BackgroundStachybotrys 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.ResultsTo 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.ConclusionsOur 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】

Unknown   
© Hu et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.