Cargando…

Colchicine inhibits ROS generation in response to glycoprotein VI stimulation

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pennings, G. J., Reddel, C. J., Traini, M., Campbell, H., Chen, V., Kritharides, L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184800/
https://www.ncbi.nlm.nih.gov/pubmed/34099810
http://dx.doi.org/10.1038/s41598-021-91409-7
_version_ 1783704653448347648
author Pennings, G. J.
Reddel, C. J.
Traini, M.
Campbell, H.
Chen, V.
Kritharides, L.
author_facet Pennings, G. J.
Reddel, C. J.
Traini, M.
Campbell, H.
Chen, V.
Kritharides, L.
author_sort Pennings, G. J.
collection PubMed
description 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, P2Y(12) 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 (H(2)DCF-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 Online
Article
Text
id pubmed-8184800
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-81848002021-06-08 Colchicine inhibits ROS generation in response to glycoprotein VI stimulation Pennings, G. J. Reddel, C. J. Traini, M. Campbell, H. Chen, V. Kritharides, L. Sci Rep Article 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, P2Y(12) 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 (H(2)DCF-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. Nature Publishing Group UK 2021-06-07 /pmc/articles/PMC8184800/ /pubmed/34099810 http://dx.doi.org/10.1038/s41598-021-91409-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Pennings, G. J.
Reddel, C. J.
Traini, M.
Campbell, H.
Chen, V.
Kritharides, L.
Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title 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_short Colchicine inhibits ROS generation in response to glycoprotein VI stimulation
title_sort colchicine inhibits ros generation in response to glycoprotein vi stimulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184800/
https://www.ncbi.nlm.nih.gov/pubmed/34099810
http://dx.doi.org/10.1038/s41598-021-91409-7
work_keys_str_mv AT penningsgj colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation
AT reddelcj colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation
AT trainim colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation
AT campbellh colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation
AT chenv colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation
AT kritharidesl colchicineinhibitsrosgenerationinresponsetoglycoproteinvistimulation