title: Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation.
abstract: Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF.
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Simon
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
authors.forename: Klemen
authors.initials: K
authors.lastname: Ziberna
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK barbara.casadei@cardiov.ox.ac.uk.
authors.forename: Barbara
authors.initials: B
authors.lastname: Casadei
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species
keywords: Antioxidants; Arrhythmia; Heart; Hydrogen peroxide; Nitric oxide; Subcellular localization