title: Redox control of cardiac remodeling in atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a potential cause of thromboembolic events. AF induces significant changes in the electrophysiological properties of atrial myocytes and causes alterations in the structure, metabolism, and function of the atrial tissue. The molecular basis for the development of structural atrial remodeling of fibrillating human atria is still not fully understood. However, increased production of reactive oxygen or nitrogen species (ROS/RNS) and the activation of specific redox-sensitive signaling pathways observed both in patients with and animal models of AF are supposed to contribute to development, progression and self-perpetuation of AF.
  
  
  METHODS
  The present review summarizes the sources and targets of ROS/RNS in the setting of AF and focuses on key redox-sensitive signaling pathways that are implicated in the pathogenesis of AF and function either to aggravate or protect from disease.
  
  
  CONCLUSIONS
  NADPH oxidases and various mitochondrial monooxygenases are major sources of ROS during AF. Besides direct oxidative modification of e.g. ion channels and ion handling proteins that are crucially involved in action potential generation and duration, AF leads to the reversible activation of redox-sensitive signaling pathways mediated by activation of redox-regulated proteins including Nrf2, NF-κB, and CaMKII. Both processes are recognized to contribute to the formation of a substrate for AF and, thus, to increase AF inducibility and duration.
  
  
  CONCLUSIONS
  AF is a prevalent disease and due to the current demographic developments its socio-economic relevance will further increase. Improving our understanding of the role that ROS and redox-related (patho)-mechanisms play in the development and progression of AF may allow the development of a targeted therapy for AF that surpasses the efficacy of previous general anti-oxidative strategies. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17487 Greifswald, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wolke
authors.affiliation: EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.affiliation: EUTRAF Working Group: Molecular Electrophysiology, University Hospital Magdeburg, D-39120 Magdeburg, Germany; Department of Cardiology and Intensive Care Medicine, St. Vincenz-Hospital, D-33098 Paderborn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17487 Greifswald, Germany. Electronic address: uwe.lendeckel@uni-greifswald.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
keywords: Atrial fibrillation; Atrial remodeling; ROS; Redox-regulation