Colchicine inhibits ROS generation in response to glycoprotein VI stimulation

Abstract Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activat...

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Autores principales:	G. J. Pennings, C. J. Reddel, M. Traini, H. Campbell, V. Chen, L. Kritharides
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69baf5f047a54ffbb5a37f94d6bc1837
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spelling	oai:doaj.org-article:69baf5f047a54ffbb5a37f94d6bc18372021-12-02T17:52:26ZColchicine inhibits ROS generation in response to glycoprotein VI stimulation10.1038/s41598-021-91409-72045-2322https://doaj.org/article/69baf5f047a54ffbb5a37f94d6bc18372021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91409-7https://doaj.org/toc/2045-2322Abstract Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y12 receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (H2DCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist). Other platelet activation pathways including P-selectin expression, GPIIb/IIIa conformational change and procoagulant platelet formation (GSAO+/CD62P+) (flow cytometry) were inhibited with higher concentrations of colchicine known to inhibit microtubule depolymerization. Pathway specific mechanisms of action of colchicine on platelets, including modulation of the GPVI receptor pathway at low concentrations, may contribute to its protective role in CAD.G. J. PenningsC. J. ReddelM. TrainiH. CampbellV. ChenL. KritharidesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q G. J. Pennings C. J. Reddel M. Traini H. Campbell V. Chen L. Kritharides Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
description	Abstract Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y12 receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (H2DCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist). Other platelet activation pathways including P-selectin expression, GPIIb/IIIa conformational change and procoagulant platelet formation (GSAO+/CD62P+) (flow cytometry) were inhibited with higher concentrations of colchicine known to inhibit microtubule depolymerization. Pathway specific mechanisms of action of colchicine on platelets, including modulation of the GPVI receptor pathway at low concentrations, may contribute to its protective role in CAD.
format	article
author	G. J. Pennings C. J. Reddel M. Traini H. Campbell V. Chen L. Kritharides
author_facet	G. J. Pennings C. J. Reddel M. Traini H. Campbell V. Chen L. Kritharides
author_sort	G. J. Pennings
title	Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_short	Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_full	Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_fullStr	Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_full_unstemmed	Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_sort	colchicine inhibits ros generation in response to glycoprotein vi stimulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69baf5f047a54ffbb5a37f94d6bc1837
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Colchicine inhibits ROS generation in response to glycoprotein VI stimulation

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