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Journal articles
Atrial fibrillation is associated with hypermethylation in human left atrium, and treatment with decitabine reduces atrial tachyarrhythmias in spontaneously hypertensive rats
R. Doñate Puertas
1
E. Meugnier
2
C. Romestaing
3
C. Rey
4
E. Morel
5
J. Lachuer
6
N. Gadot
7
A. Scridon
8
C. Julien
F. Tronc
B. Chapuis
C. Valla
9
A. Janin
9
Luciano Pirola
2
A. Mejat
10
S. Rome
2
Philippe Chevalier
11
7
ANIPATH
R. Doñate Puertas 1
Author
E. Meugnier 2
Mail :
Author IdHAL : emmanuelle-meugnier ORCID : https://orcid.org/0000-0002-2291-7691
C. Romestaing 3
Author
C. Rey 4
Author
Philippe Chevalier 11
Author
2
CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition (Faculté de Médecine Lyon Sud - BP 12 - 165 Chemin du Grand Revoyet - 69921 Oullins cedex INSA, Bât. IMBL, La Doua - 11 Avenue Jean Capelle - 69621 Villeurbanne Cedex - France)
- INRA - Institut National de la Recherche Agronomique : UMR1397 (France)
- UCBL - Université Claude Bernard Lyon 1 : UM92 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSA Lyon - Institut National des Sciences Appliquées de Lyon (20 Avenue Albert Einstein,
69621 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSA - Institut National des Sciences Appliquées (France)
- HCL - Hospices Civils de Lyon (3 Quai des Célestins 69002 Lyon - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1060 (101, rue de Tolbiac, 75013 Paris - France)
3
LEHNA - Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (Université Claude Bernard Lyon 1
3-6, rue Raphaël Dubois - Bâtiments Darwin C & Forel, 69622 Villeurbanne Cedex
43, Boulevard du 11 novembre 1918
ENTPE
3, rue Maurice Audin
69518 Vaulx-en-Velin - France)
- INRA - Institut National de la Recherche Agronomique : USC1369 (France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- ENTPE - École Nationale des Travaux Publics de l'État (3, rue Maurice Audin - 69518 Vaulx-en-Velin Cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5023 (France)
4
ProfilXpert, Univ-US7 INSERM (France)
- Santé Lyon Est - Louis Léopold Ollier (Faculté de Médecine Lyon Est - Site Laennec - 7-11 rue Guillaume Paradin 69372 Lyon Cedex 08 - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : US7 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMS3453 (France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
5
Rhythmology Unit Louis Pradel Cardiology Hospital (France)
- HCL - Hospices Civils de Lyon (3 Quai des Célestins 69002 Lyon - France)
6
ProfileXpert (Université Lyon 1, Bron - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U842 (101, rue de Tolbiac, 75013 Paris - France)
9
INMG - Institut NeuroMyoGène (Bâtiment Gregor Mendel
16 Rue Raphel Dubois
69622 Villeurbanne - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5310 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1217 (101, rue de Tolbiac, 75013 Paris - France)
10
LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule (Ecole Normale Supérieure
46 Allée d'Italie
69364 Lyon Cedex 07 - France)
- ENS Lyon - École normale supérieure - Lyon (15 parvis René Descartes - BP 7000 - 69342 Lyon Cedex 07 - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1210 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 5239 (France)
11
Unité de Cardiologie et Soins Intensifs (France)
- HCL - Hospices Civils de Lyon (3 Quai des Célestins 69002 Lyon - France)
Abstract : Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process ‘‘anatomical structure morphogenesis’’ contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis). We then focused the study on Pitx2 (paired-like homeodomain 2), being the most altered transcription factor in LA from AF patients and from which compelling evidence have indicated that its reduced expression can be considered as a marker for the disease. In addition, its expression was inversely correlated with LA size. We demonstrated that AF is associ- ated with Pitx2 promoter hypermethylation both in humans and arrhythmic aging spontaneously hypertensive rats. Chronic administration of a DNA methylation inhib- itor (ie, 5-Aza-20-deoxycitidine) improved ECG arrhythmic profiles and superoxide dismutase activities and reduced fibrosis in the left ventricle of spontaneously hyper- tensive rats. Taken together, these data support the notion that AF is associated with epigenetic changes in LA and provide a proof-of-concept that hypomethylating agents have to be considered in the treatment of atrial arrhythmias
Document type :
Journal articles
Domain :
Complete list of metadatas
https://hal-sde.archives-ouvertes.fr/hal-01621517
Contributor : Nathalie Lyvet <>
Submitted on : Monday, October 23, 2017 - 3:45:05 PM
Last modification on : Wednesday, May 27, 2020 - 3:37:24 AM
Contributor : Nathalie Lyvet <>
Submitted on : Monday, October 23, 2017 - 3:45:05 PM
Last modification on : Wednesday, May 27, 2020 - 3:37:24 AM
Identifiers
- HAL Id : hal-01621517, version 1
- DOI : 10.1016/j.trsl.2017.03.004
- PRODINRA : 408470
- PUBMED : 28427903
- WOS : 000402224400006
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Citation
R. Doñate Puertas, E. Meugnier, C. Romestaing, C. Rey, E. Morel, et al.. Atrial fibrillation is associated with hypermethylation in human left atrium, and treatment with decitabine reduces atrial tachyarrhythmias in spontaneously hypertensive rats. Translational Research, The Journal of Laboratory and Clinical Medicine, Elsevier, 2017, 184, pp.57 - 67.e5. ⟨10.1016/j.trsl.2017.03.004⟩. ⟨hal-01621517⟩
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