Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation
- 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
Article and author information
Author details
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.
Reviewing Editor
- Noriaki Emoto, Kobe Pharmaceutical University, Japan
Publication history
- Preprint posted: April 30, 2019 (view preprint)
- Received: June 22, 2020
- Accepted: December 21, 2021
- Accepted Manuscript published: December 23, 2021 (version 1)
- 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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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
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