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

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 plasm...

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Autores principales: Hu, Weimin, Narasaki, Ritsuko, Nishimura, Naoko, Hasumi, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310738/
https://www.ncbi.nlm.nih.gov/pubmed/22230042
http://dx.doi.org/10.1186/1477-9560-10-2
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author Hu, Weimin
Narasaki, Ritsuko
Nishimura, Naoko
Hasumi, Keiji
author_facet Hu, Weimin
Narasaki, Ritsuko
Nishimura, Naoko
Hasumi, Keiji
author_sort Hu, Weimin
collection PubMed
description 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-α(2)-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.
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spelling pubmed-33107382012-03-23 SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats Hu, Weimin Narasaki, Ritsuko Nishimura, Naoko Hasumi, Keiji Thromb J Original Basic Research 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-α(2)-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. BioMed Central 2012-01-09 /pmc/articles/PMC3310738/ /pubmed/22230042 http://dx.doi.org/10.1186/1477-9560-10-2 Text en Copyright ©2012 Hu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Original Basic Research
Hu, Weimin
Narasaki, Ritsuko
Nishimura, Naoko
Hasumi, Keiji
SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title_full SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title_fullStr SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title_full_unstemmed SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title_short SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
title_sort smtp (stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats
topic Original Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310738/
https://www.ncbi.nlm.nih.gov/pubmed/22230042
http://dx.doi.org/10.1186/1477-9560-10-2
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