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Int J Cardiol. 2015;187:604-13. doi: 10.1016/j.ijcard.2015.03.072. Epub 2015 Mar 23.

Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria.

Author information

1
University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
2
University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany.
3
EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany.
4
EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany; Cardiology and Intensive Care Medicine, St. Vincenz-Hospital, Paderborn, Germany.
5
University Medicine Greifswald, Department of Cardiology, Greifswald, Germany.
6
Dr. Guth Clinics, Dept. of Cardiovascular Surgery, Karlsburg, Germany.
7
University Medicine Greifswald, Department of Pathology, Greifswald, Germany.
8
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
9
Hôpital Cardiologique du Haut Lévêque, Université Victor-Segalen Bordeaux II, Pessac, France.
10
Sorbonne Universités, UPMC University Paris 06, UMR_S 1166 I, ICAN, Paris, France.
11
University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany. Electronic address: uwe.lendeckel@uni-greifswald.de.

Abstract

PURPOSE:

Atrial fibrillation (AF) has been associated with increased volumes of epicardial fat and atrial adipocyte accumulation. Underlying mechanisms are not well understood. This study aims to identify rapid atrial pacing (RAP)/AF-dependent changes in atrial adipocyte/adipositas-related gene expression (AARE).

METHODS:

Right atrial (RA) and adjacent epicardial adipose tissue (EAT) samples were obtained from 26 patients; 13 with AF, 13 in sinus rhythm (SR). Left atrial (LA) samples were obtained from 9 pigs (5 RAP, 4 sham-operated controls). AARE was analyzed using microarrays and RT-qPCR. The impact of diabetes/obesity on gene expression was additionally determined in RA samples (RAP ex vivo and controls) from 3 vs. 6 months old ZDF rats.

RESULTS:

RAP in vivo of pigs resulted in substantial changes of AARE, with 66 genes being up- and 53 down-regulated on the mRNA level. Differential expression during adipocyte differentiation was confirmed using 3T3-L1 cells. In patients with AF (compared to SR), a comparable change in RA mRNA levels concerned a fraction of genes only (RETN, IGF1, HK2, PYGM, LOX, and NR4A3). RA and EAT were affected by AF to a different extent. In patients, concomitant disease contributes to AARE changes.

CONCLUSIONS:

RAP, and to lesser extent AF, provoke significant changes in atrial AARE. In chronic AF, activation of this gene panel is very likely mediated by AF itself, AF risk factors and concomitant diseases. This may facilitate the development of an AF substrate by increasing atrial ectopic fat and fat infiltration of the atrial myocardium.

KEYWORDS:

Adipocyte differentiation; Atrial adipositas; Atrial fibrillation; Structural remodeling

PMID:
25863735
DOI:
10.1016/j.ijcard.2015.03.072
[Indexed for MEDLINE]

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