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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
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
_version_ 1785076269179731968
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
work_keys_str_mv AT mauersbergercarina lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT sagerhendrikb lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT wobstjana lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT dangtanan lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT lambrechtlaura lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT koplevsimon lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT strothmarlene lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT bettaganoomen lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT schlossmannjens lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT wunderfrank lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT friebeandreas lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT bjorkegrenjohanlm lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT dietzlisa lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT maassannel lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT vandervorstemielpc lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT sandnerpeter lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT soehnleinoliver lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT schunkertheribert lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation
AT kesslerthorsten lossofsolubleguanylylcyclaseinplateletscontributestoatheroscleroticplaqueformationandvascularinflammation