title: Protective role of heme oxygenase-1 in atrial remodeling.
abstract: Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development.
authors: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin Road, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Yung-Hsin
authors: YH
authors: Yeh
authors: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin Road, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Lung-An
authors: LA
authors: Hsu
authors: Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, National Yang-Ming University College of Medicine, Taipei, Taiwan, ROC.
authors: Ying-Hwa
authors: YH
authors: Chen
authors: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin Road, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
authors: Chi-Tai
authors: CT
authors: Kuo
authors: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors: Gwo-Jyh
authors: GJ
authors: Chang
authors: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin Road, Kwei-Shan, Tao-Yuan, Taiwan, ROC. wjchen@adm.cgmh.org.tw.
authors: Wei-Jan
authors: WJ
authors: Chen
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology; D064752:Atrial Remodeling / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Atrial fibrillation; Atrial fibrosis; Heme oxygenase-1; Nrf2 nuclear factor erythroid-2-related factor 2; Oxidative stress