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Changes in AMPKα and Ubiquitin Ligases in Myocyte Reverse Remodeling after Surgical Ventricular Reconstruction in rats with ischemic cardiomyopathy

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Abstract

Background

The change in myocardial protein degradation systems after ventricular unloading has been unknown. We aimed to evaluate the anti-hypertrophic protein adenosine monophosphate-activated protein kinase (AMPK) and two major protein degradation systems (ubiquitin proteasome system and autophagy) in a model of surgical ventricular reconstruction (SVR) in rats with ischemic cardiomyopathy.

Methods and Results

Rats were randomized into the following groups: sham/sham (control group), myocardial infarction (MI)/sham (sham group) and MI/SVR (SVR group), with an interval of 4 weeks. Two (early, n = 5 for each) and 28 days (late, n = 5 for each) after SVR, ventricular size, and wall stress were assessed. Myocyte area, protein expression of AMPKα and autophagy markers, and gene expression of ubiquitin ligases (Atrogin-1 and Murf-1) were evaluated in the late phase. In the early phase, left ventricular dimensions and wall stress were smaller in the SVR group than in the sham group, whereas they were comparable in the late period. Myocyte area in the SVR group was reduced to the value in the control group, while it was larger in the sham group than in the control group. Total-AMPKα, p-AMPKα, and AMPKα phosphorylation rates were higher, and Atrogin-1 and Murf-1 were lower in the SVR group than in the sham group, while the autophagy markers were not different between the groups. p-AMPKα had strong negative correlations with myocyte area, Atrogin-1, and Murf-1.

Conclusions

In myocyte reverse remodeling after SVR, AMPKα phosphorylation increased in association with reduced gene expression of ubiquitin ligases.

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Acknowledgements

We would like to thank Editage for English language editing.

Funding

This work was partly supported by Japan Heart Foundation Research Grant 2015 [to Yasushige Shingu]; Mochida Memorial Foundation for Medical and Pharmaceutical Research 2016 [to Yasushige Shingu].

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Authors and Affiliations

  1. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Yasushige Shingu, Tetsuya Hieda & Satoru Wakasa

  2. Department of Cardiovascular Surgery, Obihiro Kosei Hospital, Obihiro, Japan

    Satoshi Sugimoto

  3. Department of Cardiovascular Surgery, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan

    Hidetsugu Asai

  4. Department of Cardiovascular Surgery, Kinikyo Chuo Hospital, Sapporo, Japan

    Tomoji Yamakawa

  5. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, 060-8638, Kitaku, Sapporo, Japan

    Yasushige Shingu

Authors
  1. Yasushige Shingu
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  2. Tetsuya Hieda
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  3. Satoshi Sugimoto
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  4. Hidetsugu Asai
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  5. Tomoji Yamakawa
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  6. Satoru Wakasa
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yasushige Shingu, Tetsuya Hieda, Satoshi Sugimoto, Hidetsugu Asai, and Tomoji Yamakawa. Manuscript revision was performed by Satoru Wakasa. The first draft of the manuscript was written by Yasushige Shingu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yasushige Shingu.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

All procedures were approved by the National University Corporation Hokkaido University Animal Research Committee and consistent with the Guide for the Care and Use of Laboratory Animals, published by the US National Institute of Health (NIH publication No. 85 − 23, revised 1996).

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Shingu, Y., Hieda, T., Sugimoto, S. et al. Changes in AMPKα and Ubiquitin Ligases in Myocyte Reverse Remodeling after Surgical Ventricular Reconstruction in rats with ischemic cardiomyopathy. Mol Biol Rep 49, 4885–4892 (2022). https://doi.org/10.1007/s11033-022-07347-8

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  • DOI: https://doi.org/10.1007/s11033-022-07347-8

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