Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation
Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr(−/−) mice contributes...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361702/ https://www.ncbi.nlm.nih.gov/pubmed/37484062 http://dx.doi.org/10.1038/s44161-022-00175-w |
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author | Mauersberger, Carina Sager, Hendrik B. Wobst, Jana Dang, Tan An Lambrecht, Laura Koplev, Simon Stroth, Marlène Bettaga, Noomen Schlossmann, Jens Wunder, Frank Friebe, Andreas Björkegren, Johan L. M. Dietz, Lisa Maas, Sanne L. van der Vorst, Emiel P. C. Sandner, Peter Soehnlein, Oliver Schunkert, Heribert Kessler, Thorsten |
author_facet | Mauersberger, Carina Sager, Hendrik B. Wobst, Jana Dang, Tan An Lambrecht, Laura Koplev, Simon Stroth, Marlène Bettaga, Noomen Schlossmann, Jens Wunder, Frank Friebe, Andreas Björkegren, Johan L. M. Dietz, Lisa Maas, Sanne L. van der Vorst, Emiel P. C. Sandner, Peter Soehnlein, Oliver Schunkert, Heribert Kessler, Thorsten |
author_sort | Mauersberger, Carina |
collection | PubMed |
description | Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr(−/−) mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. I mp or ta ntly, p ha rm ac ol ogical sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr(−/−) mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD. |
format | Online Article Text |
id | pubmed-10361702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-103617022023-07-21 Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation Mauersberger, Carina Sager, Hendrik B. Wobst, Jana Dang, Tan An Lambrecht, Laura Koplev, Simon Stroth, Marlène Bettaga, Noomen Schlossmann, Jens Wunder, Frank Friebe, Andreas Björkegren, Johan L. M. Dietz, Lisa Maas, Sanne L. van der Vorst, Emiel P. C. Sandner, Peter Soehnlein, Oliver Schunkert, Heribert Kessler, Thorsten Nat Cardiovasc Res Article Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr(−/−) mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. I mp or ta ntly, p ha rm ac ol ogical sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr(−/−) mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD. 2022-12 2022-12-12 /pmc/articles/PMC10361702/ /pubmed/37484062 http://dx.doi.org/10.1038/s44161-022-00175-w Text en https://creativecommons.org/licenses/by/4.0/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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mauersberger, Carina Sager, Hendrik B. Wobst, Jana Dang, Tan An Lambrecht, Laura Koplev, Simon Stroth, Marlène Bettaga, Noomen Schlossmann, Jens Wunder, Frank Friebe, Andreas Björkegren, Johan L. M. Dietz, Lisa Maas, Sanne L. van der Vorst, Emiel P. C. Sandner, Peter Soehnlein, Oliver Schunkert, Heribert Kessler, Thorsten Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title | Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title_full | Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title_fullStr | Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title_full_unstemmed | Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title_short | Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
title_sort | loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361702/ https://www.ncbi.nlm.nih.gov/pubmed/37484062 http://dx.doi.org/10.1038/s44161-022-00175-w |
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