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Protective role of heme oxygenase-1 in atrial remodeling

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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.

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Acknowledgments

We thank Dr. Lee-Young Chau for her technical assistance in measuring HO activity.

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    Authors and Affiliations

    1. Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin Road, Kwei-Shan, Tao-Yuan, Taiwan, ROC

      Yung-Hsin Yeh, Lung-An Hsu, Chi-Tai Kuo & Wei-Jan Chen

    2. Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, National Yang-Ming University College of Medicine, Taipei, Taiwan, ROC

      Ying-Hwa Chen

    3. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan, ROC

      Gwo-Jyh Chang

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    1. Yung-Hsin Yeh
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    Correspondence to Wei-Jan Chen.

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    This work was supported by the Chang Gung Research Grant Foundation (CMRPG 3A0571-3, 3A0641-3, 391111, 3B0991-3, 3C062, and 13D1371-3); and the National Science Council Grant (NSC 99-2314-B-182A-050-MY2, NSC100-2314-B-182-049, and 102-2314-B-182A-053-MY3).

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    Y.-H. Yeh and L.-A. Hsu contribute equally to this work.

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    Yeh, YH., Hsu, LA., Chen, YH. et al. Protective role of heme oxygenase-1 in atrial remodeling. Basic Res Cardiol 111, 58 (2016). https://doi.org/10.1007/s00395-016-0577-y

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