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Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling
While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277802/ https://www.ncbi.nlm.nih.gov/pubmed/34257332 http://dx.doi.org/10.1038/s41598-021-93755-y |
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author | Puhl, Sarah-Lena Hilby, Michael Kohlhaas, Michael Keidel, Linus M. Jansen, Yvonne Hristov, Michael Schindler, Jakob Maack, Christoph Steffens, Sabine |
author_facet | Puhl, Sarah-Lena Hilby, Michael Kohlhaas, Michael Keidel, Linus M. Jansen, Yvonne Hristov, Michael Schindler, Jakob Maack, Christoph Steffens, Sabine |
author_sort | Puhl, Sarah-Lena |
collection | PubMed |
description | While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55−/− and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28 days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55−/− deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55−/− hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up-regulation of extracellular matrix (ECM) factors 3 days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling. |
format | Online Article Text |
id | pubmed-8277802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82778022021-07-15 Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling Puhl, Sarah-Lena Hilby, Michael Kohlhaas, Michael Keidel, Linus M. Jansen, Yvonne Hristov, Michael Schindler, Jakob Maack, Christoph Steffens, Sabine Sci Rep Article While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55−/− and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28 days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55−/− deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55−/− hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up-regulation of extracellular matrix (ECM) factors 3 days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling. Nature Publishing Group UK 2021-07-13 /pmc/articles/PMC8277802/ /pubmed/34257332 http://dx.doi.org/10.1038/s41598-021-93755-y 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 Puhl, Sarah-Lena Hilby, Michael Kohlhaas, Michael Keidel, Linus M. Jansen, Yvonne Hristov, Michael Schindler, Jakob Maack, Christoph Steffens, Sabine Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title | Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title_full | Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title_fullStr | Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title_full_unstemmed | Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title_short | Haematopoietic and cardiac GPR55 synchronize post-myocardial infarction remodelling |
title_sort | haematopoietic and cardiac gpr55 synchronize post-myocardial infarction remodelling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277802/ https://www.ncbi.nlm.nih.gov/pubmed/34257332 http://dx.doi.org/10.1038/s41598-021-93755-y |
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