title: Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria.
abstract: OBJECTIVE
  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.
authors: University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors: R K
authors: RK
authors: Chilukoti
authors: University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany.
authors: A
authors: A
authors: Giese
authors: University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany.
authors: W
authors: W
authors: Malenke
authors: University Medicine Greifswald, Ernst-Moritz-Arndt-University Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors: G
authors: G
authors: Homuth
authors: EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany.
authors: A
authors: A
authors: Bukowska
authors: EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany; Cardiology and Intensive Care Medicine, St. Vincenz-Hospital, Paderborn, Germany.
authors: A
authors: A
authors: Goette
authors: University Medicine Greifswald, Department of Cardiology, Greifswald, Germany.
authors: S B
authors: SB
authors: Felix
authors: Dr. Guth Clinics, Dept. of Cardiovascular Surgery, Karlsburg, Germany.
authors: J
authors: J
authors: Kanaan
authors: Dr. Guth Clinics, Dept. of Cardiovascular Surgery, Karlsburg, Germany.
authors: H-G
authors: HG
authors: Wollert
authors: University Medicine Greifswald, Department of Pathology, Greifswald, Germany.
authors: K
authors: K
authors: Evert
authors: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors: S
authors: S
authors: Verheule
authors: Hôpital Cardiologique du Haut Lévêque, Université Victor-Segalen Bordeaux II, Pessac, France.
authors: P
authors: P
authors: Jais
authors: Sorbonne Universités, UPMC University Paris 06, UMR_S 1166 I, ICAN, Paris, France.
authors: S N
authors: SN
authors: Hatem
authors: University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany. Electronic address: uwe.lendeckel@uni-greifswald.de.
authors: U
authors: U
authors: Lendeckel
authors: University Medicine Greifswald, Institute of Medical Biochemistry and Molecular Biology, Greifswald, Germany.
authors: C
authors: C
authors: Wolke
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000368:Aged; D000818:Animals; D020517:Atrial Appendage / Q000378:metabolism; D001281:Atrial Fibrillation / Q000235:genetics* / Q000628:therapy*; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010496:Pericardium / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine
chemical_list: D016326:Extracellular Matrix Proteins
keywords: Adipocyte differentiation; Atrial adipositas; Atrial fibrillation; Structural remodeling