Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation

  1. Ienglam Lei
  2. Shuo Tian
  3. Wenbin Gao
  4. Liu Liu
  5. Yijing Guo
  6. Paul Tang
  7. Eugene Chen
  8. Zhong Wang  Is a corresponding author
  1. University of Michigan-Ann Arbor, United States

Abstract

Myocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart repair has been poorly explored. Here, we examined the effect of different carbon sources that are involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA by sodium octanoate (8C) significantly improved heart function in ischemia reperfusion (I/R) rats. Mechanistically, 8C reduced I/R injury by promoting histone acetylation which in turn activated the expression of antioxidant genes and inhibited cardiomyocyte (CM) apoptosis. Furthermore, we elucidated that 8C-promoted histone acetylation and heart repair were carried out by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetyltransferase Kat2a, suggesting that 8C dramatically improves cardiac function mainly through metabolic acetyl-CoA-mediated histone acetylation. Therefore, our study uncovers an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and Kat2a to combat heart injury.

Data availability

The RNA-seq data have been deposited in Gene Expression Omnibus with the accession code GSE132515

The following data sets were generated

Article and author information

Author details

  1. Ienglam Lei

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Shuo Tian

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wenbin Gao

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Liu Liu

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yijing Guo

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul Tang

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Eugene Chen

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhong Wang

    Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States
    For correspondence
    zhongw@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8720-4609

Funding

National Institutes of Health (HL109054)

  • Zhong Wang

National Institutes of Health (HL139735)

  • Zhong Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Noriaki Emoto, Kobe Pharmaceutical University, Japan

Ethics

Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committee of the University of Michigan (PRO00009606) and were performed in accordance with the recommendations of the American Association for the Accreditation of Laboratory Animal Care.

Version history

  1. Preprint posted: April 30, 2019 (view preprint)
  2. Received: June 22, 2020
  3. Accepted: December 21, 2021
  4. Accepted Manuscript published: December 23, 2021 (version 1)
  5. Version of Record published: January 17, 2022 (version 2)

Copyright

© 2021, Lei et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ienglam Lei
  2. Shuo Tian
  3. Wenbin Gao
  4. Liu Liu
  5. Yijing Guo
  6. Paul Tang
  7. Eugene Chen
  8. Zhong Wang
(2021)
Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation
eLife 10:e60311.
https://doi.org/10.7554/eLife.60311

Share this article

https://doi.org/10.7554/eLife.60311

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