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Aliskiren protecting atrial structural remodeling from rapid atrial pacing in a canine model

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Abstract

Atrial fibrillation (AF) contributing to the increasing mortality risk is the most common disease in clinical practice. Owing to the side effects and relative inefficacy of current antiarrhythmic drugs, some research focuses on renin–angiotensin–aldosterone system (RAS) for finding out the new treatment of AF. The purpose of this study is to confirm whether aliskiren as a proximal inhibitor of renin, which completely inhibits RAS, has beneficial effects on atrial structural remodeling in AF. In this study, rapid atrial pacing was induced at 500 beats per minute for 2 weeks in a canine model. A different dose of aliskiren was given orally for 2 weeks before rapid atrial pacing. HE staining and Masson’s staining were used for analysis of myocardial fibrosis. TGF-β1, signal pathways, and pro-inflammatory cytokines were shown for the mechanism of structural remodeling after the treatment of aliskiren. Serious atrial fibrosis was induced by rapid atrial pacing, followed by the elevated TGF-β1, upregulated MEK and ERK1/2, and increased inflammatory factors. Aliskiren could apparently improve myocardial fibrosis by reducing the expression of TGF-β1, inhibiting MEK and ERK1/2 signal pathways, and decreasing IL-18 and TLR4 in both serum and atrial tissue. In conclusion, aliskiren could prevent atrial structural remodeling from rapid atrial pacing for 2 weeks. Aliskiren may play a potential beneficial role in the treatment of AF induced by rapid atrial pacing.

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Acknowledgments

This work was supported by the Program of Natural Science Foundation of China (no. 81370300) and the China Education Ministry Colleges and Universities Special Scientific Research Foundation for Doctoral Advisor Class (no. 20121202110004).

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Authors and Affiliations

  1. Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China

    Zhiqiang Zhao, Yan Chen, Xinghua Wang, Jian Li, Wansong Yang, Lijun Cheng, Tong Liu, Enzhao Liu & Guangping Li

  2. Department of Pharmacology, Tianjin Medical University, Tianjin, People’s Republic of China

    Yan Chen

  3. Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China

    Weimin Li

Authors
  1. Zhiqiang Zhao
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  2. Yan Chen
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  3. Weimin Li
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  4. Xinghua Wang
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  5. Jian Li
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  6. Wansong Yang
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  7. Lijun Cheng
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  8. Tong Liu
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  9. Enzhao Liu
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  10. Guangping Li
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Corresponding author

Correspondence to Guangping Li.

Ethics declarations

The animals we used in this experiment were approved by the Experimental Animal Administration Committee of Tianjin Medical University and Tianjin Municipal Commission for Experimental Animal Control. The animals are provided by Tianjin Center for Drug Safety Assessment and Research, Tianjin Institute of Pharmaceutical Research (SYXK 2011-0005).

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The authors declare that they have no conflict of interest.

Additional information

Zhiqiang Zhao and Yan Chen contributed equally to the work and should be regarded as co-first authors.

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Zhao, Z., Chen, Y., Li, W. et al. Aliskiren protecting atrial structural remodeling from rapid atrial pacing in a canine model. Naunyn-Schmiedeberg's Arch Pharmacol 389, 863–871 (2016). https://doi.org/10.1007/s00210-016-1249-z

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  • DOI: https://doi.org/10.1007/s00210-016-1249-z

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