title: Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria.
abstract: Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF.
  
  
  
  Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria.
  
  
  
  Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF.
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Haemers
authors.affiliation: Sorbonne Université Paris 06, UMR_S1166 team Cardiac Electrophysiology, Paris, France.|INSERM UMR_S1166 team Cardiac Electrophysiology, Paris, France.|Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital and Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Hadhami
authors.initials: H
authors.lastname: Hamdi
authors.affiliation: Laboratory for Vascular Translational Science, INSERM UMR_S1148, Hôpital Xavier Bichat, Paris, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Guedj
authors.affiliation: Sorbonne Université Paris 06, UMR_S1166 team Cardiac Electrophysiology, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Suffee
authors.affiliation: INSERM UMR_S1166 team Cardiac Electrophysiology, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Farahmand
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Natasa
authors.initials: N
authors.lastname: Popovic
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Claus
authors.affiliation: INSERM UMR_S1166 team Cardiac Electrophysiology, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: LePrince
authors.affiliation: Laboratory for Vascular Translational Science, INSERM UMR_S1148, Hôpital Xavier Bichat, Paris, France.
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
authors.affiliation: Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Jalife
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wolke
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.affiliation: Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jaïs
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Willems
authors.affiliation: Sorbonne Université Paris 06, UMR_S1166 team Cardiac Electrophysiology, Paris, France stephane.hatem@upmc.fr.|INSERM UMR_S1166 team Cardiac Electrophysiology, Paris, France.|Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital and Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000473:pathology*; D064752:Atrial Remodeling / Q000502:physiology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D006325:Heart Atria; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D009206:Myocardium / Q000473:pathology*; D012189:Retrospective Studies; D012756:Sheep
keywords: Adipose tissue; Atrial fibrillation; Atrial myocardium; Fibrosis