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Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling
Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by st...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110994/ https://www.ncbi.nlm.nih.gov/pubmed/37081960 http://dx.doi.org/10.3389/fphar.2023.1083910 |
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author | Wilson, Claire Zi, Min Smith, Matthew Hussain, Munir D’Souza, Alicia Dobrzynski, Halina Boyett, Mark R. |
author_facet | Wilson, Claire Zi, Min Smith, Matthew Hussain, Munir D’Souza, Alicia Dobrzynski, Halina Boyett, Mark R. |
author_sort | Wilson, Claire |
collection | PubMed |
description | Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure. |
format | Online Article Text |
id | pubmed-10110994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101109942023-04-19 Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling Wilson, Claire Zi, Min Smith, Matthew Hussain, Munir D’Souza, Alicia Dobrzynski, Halina Boyett, Mark R. Front Pharmacol Pharmacology Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure. Frontiers Media S.A. 2023-04-04 /pmc/articles/PMC10110994/ /pubmed/37081960 http://dx.doi.org/10.3389/fphar.2023.1083910 Text en Copyright © 2023 Wilson, Zi, Smith, Hussain, D’Souza, Dobrzynski and Boyett. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Wilson, Claire Zi, Min Smith, Matthew Hussain, Munir D’Souza, Alicia Dobrzynski, Halina Boyett, Mark R. Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title | Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title_full | Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title_fullStr | Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title_full_unstemmed | Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title_short | Atrioventricular node dysfunction in pressure overload-induced heart failure—Involvement of the immune system and transcriptomic remodelling |
title_sort | atrioventricular node dysfunction in pressure overload-induced heart failure—involvement of the immune system and transcriptomic remodelling |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110994/ https://www.ncbi.nlm.nih.gov/pubmed/37081960 http://dx.doi.org/10.3389/fphar.2023.1083910 |
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