Atrial fibrillation in the presence and absence of heart failure enhances expression of genes involved in cardiomyocyte structure, conduction properties, fibrosis, inflammation, and endothelial dysfunction.
Atrial fibrillation
Atrial tissue samples
Gene expression
Heart failure
RNA sequencing
Journal
Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
22
09
2021
revised:
29
07
2022
accepted:
16
08
2022
pubmed:
26
8
2022
medline:
6
12
2022
entrez:
25
8
2022
Statut:
ppublish
Résumé
Little is known about genome-wide changes in the atrial transcriptome as a cause or consequence of atrial fibrillation (AF), and the effect of its common and clinically relevant comorbidity-heart failure (HF). The purpose of this study was to explore candidate disease processes for AF by investigating gene expression changes in atrial tissue samples from patients with and without AF, stratified by HF. RNA sequencing was performed in right and left atrial appendage tissue in 195 patients undergoing open heart surgery from centers participating in the CATCH-ME consortium (no history of AF, n = 91; paroxysmal AF, n = 53; persistent/permanent AF, n = 51). Analyses were stratified into patients with/without HF (n = 75/120) and adjusted for age, sex, atrial side, and a combination of clinical characteristics. We identified 35 genes associated with persistent AF compared to patients without a history of AF, both in the presence or absence of HF (false discovery rate <0.05). These were mostly novel associations, including 13 long noncoding RNAs. Genes were involved in regulation of cardiomyocyte structure, conduction properties, fibrosis, inflammation, and endothelial dysfunction. Gene set enrichment analysis identified mainly inflammatory gene sets to be enriched in AF patients without HF, and gene sets involved in cellular respiration in AF patients with HF. Analysis of atrial gene expression profiles identified numerous novel genes associated with persistent AF, in the presence or absence of HF. Interestingly, no consistent transcriptional changes were associated with paroxysmal AF, suggesting that AF-induced changes in gene expression predominate other changes.
Sections du résumé
BACKGROUND
Little is known about genome-wide changes in the atrial transcriptome as a cause or consequence of atrial fibrillation (AF), and the effect of its common and clinically relevant comorbidity-heart failure (HF).
OBJECTIVE
The purpose of this study was to explore candidate disease processes for AF by investigating gene expression changes in atrial tissue samples from patients with and without AF, stratified by HF.
METHODS
RNA sequencing was performed in right and left atrial appendage tissue in 195 patients undergoing open heart surgery from centers participating in the CATCH-ME consortium (no history of AF, n = 91; paroxysmal AF, n = 53; persistent/permanent AF, n = 51). Analyses were stratified into patients with/without HF (n = 75/120) and adjusted for age, sex, atrial side, and a combination of clinical characteristics.
RESULTS
We identified 35 genes associated with persistent AF compared to patients without a history of AF, both in the presence or absence of HF (false discovery rate <0.05). These were mostly novel associations, including 13 long noncoding RNAs. Genes were involved in regulation of cardiomyocyte structure, conduction properties, fibrosis, inflammation, and endothelial dysfunction. Gene set enrichment analysis identified mainly inflammatory gene sets to be enriched in AF patients without HF, and gene sets involved in cellular respiration in AF patients with HF.
CONCLUSION
Analysis of atrial gene expression profiles identified numerous novel genes associated with persistent AF, in the presence or absence of HF. Interestingly, no consistent transcriptional changes were associated with paroxysmal AF, suggesting that AF-induced changes in gene expression predominate other changes.
Identifiants
pubmed: 36007727
pii: S1547-5271(22)02315-3
doi: 10.1016/j.hrthm.2022.08.019
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2115-2124Subventions
Organisme : British Heart Foundation
ID : FS/13/43/30324
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/17/30/32961
Pays : United Kingdom
Informations de copyright
Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.