title: Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα.
abstract: Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF.
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Aschar-Sobbi
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: Farzad
authors.initials: F
authors.lastname: Izaddoustdar
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Korogyi
authors.affiliation: Cardiovascular Research Institute, Department of Molecular Physiology and Biophysics, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Qiongling
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics, Boston University, 700 Albany St, Boston, Massachusetts 02118-2526, USA.
authors.forename: Gerrie P
authors.initials: GP
authors.lastname: Farman
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: FengHua
authors.initials: F
authors.lastname: Yang
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: Wallace
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: David
authors.initials: D
authors.lastname: Dorian
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road East, Guelph, Ontario, Canada N1G2W1.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Simpson
authors.affiliation: Department of Physiology and Pharmacology, Western University, Medical Science Building, London, Ontario, Canada N6A5C1.
authors.forename: Jari M
authors.initials: JM
authors.lastname: Tuomi
authors.affiliation: Department of Physiology and Pharmacology, Western University, Medical Science Building, London, Ontario, Canada N6A5C1.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Jones
authors.affiliation: 1] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, 200 Elizabeth St, Toronto, Ontario, Canada M5G2C4.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Nanthakumar
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, 555 University Ave, Toronto, Ontario, Canada M5G 1X9.
authors.forename: Brian
authors.initials: B
authors.lastname: Cox
authors.affiliation: Cardiovascular Research Institute, Department of Molecular Physiology and Biophysics, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.affiliation: 1] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Division of Cardiology, St Michael's Hospital, 2300 Yonge St, Toronto, Ontario, Canada M4P1E4.
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.affiliation: 1] Department of Physiology, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [2] Department of Medicine, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8 [3] Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, 200 Elizabeth St, Toronto, Ontario, Canada M5G2C4 [4] Heart &Stroke Richard Lewar Centre of Excellence, University of Toronto, 1 King's College Cir., Toronto, Ontario, Canada M5S1A8.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Backx
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology*; D006325:Heart Atria / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases