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

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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

1. Wang Z
2. et al
(2021) Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation
NCBI Gene Expression Omnibus, GSE132515.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE132515

Article and author information

Author details

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.
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.
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.
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.
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.
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.
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.
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.

"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.

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.

Copyright

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.