Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.

Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are amon...

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Autores principales:	Elena Zavyalova, Nadezhda Samoylenkova, Alexander Revishchin, Andrey Golovin, Galina Pavlova, Alexey Kopylov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/999b92fe1837498d9e52791d049d878b
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spelling	oai:doaj.org-article:999b92fe1837498d9e52791d049d878b2021-11-25T06:01:39ZEvaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.1932-620310.1371/journal.pone.0107113https://doaj.org/article/999b92fe1837498d9e52791d049d878b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25192011/?tool=EBIhttps://doaj.org/toc/1932-6203Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are among them. RA-36, the 31-meric DNA aptamer, consists of two thrombin binding pharmacophores joined with the thymine linker. It has been shown earlier that RA-36 directly inhibits thrombin in the reaction of fibrinogen hydrolysis, and also it inhibits plasma and blood coagulation. Studies of both inhibitory and anticoagulation effects had indicated rather high species specificity of the aptamer. Further R&D of RA-36 requires exploring its efficiency in vivo. Therefore the development of a robust and adequate animal model for effective physiological studies of aptamers is in high current demand. This work is devoted to in vivo study of the antithrombotic effect of RA-36 aptamer. A murine model of thrombosis has been applied to reveal a lag and even prevention of thrombus formation when RA-36 was intravenous bolus injected in high doses of 1.4-7.1 µmol/kg (14-70 mg/kg). A comparative study of RA-36 aptamer and bivalirudin reveals that both direct thrombin inhibitors have similar antithrombotic effects for the murine model of thrombosis; though in vitro bivalirudin has anticoagulation activity several times higher compared to RA-36. The results indicate that both RA-36 aptamer and bivalirudin are direct thrombin inhibitors of different potency, but possible interactions of the thrombin-inhibitor complex with other components of blood coagulation cascade level the physiological effects for both inhibitors.Elena ZavyalovaNadezhda SamoylenkovaAlexander RevishchinAndrey GolovinGalina PavlovaAlexey KopylovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107113 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena Zavyalova Nadezhda Samoylenkova Alexander Revishchin Andrey Golovin Galina Pavlova Alexey Kopylov Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
description	Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are among them. RA-36, the 31-meric DNA aptamer, consists of two thrombin binding pharmacophores joined with the thymine linker. It has been shown earlier that RA-36 directly inhibits thrombin in the reaction of fibrinogen hydrolysis, and also it inhibits plasma and blood coagulation. Studies of both inhibitory and anticoagulation effects had indicated rather high species specificity of the aptamer. Further R&D of RA-36 requires exploring its efficiency in vivo. Therefore the development of a robust and adequate animal model for effective physiological studies of aptamers is in high current demand. This work is devoted to in vivo study of the antithrombotic effect of RA-36 aptamer. A murine model of thrombosis has been applied to reveal a lag and even prevention of thrombus formation when RA-36 was intravenous bolus injected in high doses of 1.4-7.1 µmol/kg (14-70 mg/kg). A comparative study of RA-36 aptamer and bivalirudin reveals that both direct thrombin inhibitors have similar antithrombotic effects for the murine model of thrombosis; though in vitro bivalirudin has anticoagulation activity several times higher compared to RA-36. The results indicate that both RA-36 aptamer and bivalirudin are direct thrombin inhibitors of different potency, but possible interactions of the thrombin-inhibitor complex with other components of blood coagulation cascade level the physiological effects for both inhibitors.
format	article
author	Elena Zavyalova Nadezhda Samoylenkova Alexander Revishchin Andrey Golovin Galina Pavlova Alexey Kopylov
author_facet	Elena Zavyalova Nadezhda Samoylenkova Alexander Revishchin Andrey Golovin Galina Pavlova Alexey Kopylov
author_sort	Elena Zavyalova
title	Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
title_short	Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
title_full	Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
title_fullStr	Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
title_full_unstemmed	Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.
title_sort	evaluation of antithrombotic activity of thrombin dna aptamers by a murine thrombosis model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/999b92fe1837498d9e52791d049d878b
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Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.

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