Elife. 2021 Dec 23;10. doi: 10.7554/eLife.60311. Epub 2021 Dec 23.

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

eLife

Ienglam Lei, Shuo Tian, Wenbin Gao, Liu Liu, Yijing Guo, Paul Tang, Eugene Chen, Zhong Wang

PMID: 34939931 DOI: 10.7554/eLife.60311

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.

© 2021, Lei et al.

Keywords: cell biology; mouse

Conflict of interest statement

Publication Types

• Journal Article

Grant support

• HL109054/NH/NIH HHS/United States
• HL139735/NH/NIH HHS/United States