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01-09-2016 | Original Contribution

Protective role of heme oxygenase-1 in atrial remodeling

Authors: Yung-Hsin Yeh, Lung-An Hsu, Ying-Hwa Chen, Chi-Tai Kuo, Gwo-Jyh Chang, Wei-Jan Chen

Published in: Basic Research in Cardiology | Issue 5/2016

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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Title: Protective role of heme oxygenase-1 in atrial remodeling
Authors: Yung-Hsin Yeh
Lung-An Hsu
Ying-Hwa Chen
Chi-Tai Kuo
Gwo-Jyh Chang
Wei-Jan Chen
Publication date: 01-09-2016
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2016
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-016-0577-y

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