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

eLife

Eugene Chen¹  Paul Tang¹  Wenbin Gao¹  Yijing Guo¹  Zhong Wang¹  Shuo Tian¹  Liu Liu¹  Ienglam Lei² 

[1] Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States;Faculty of Health Sciences, University of Macau, Taipa, China;Department of Cardiac Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States;

关键词: histone acetylation;    acetyl-CoA;    reactive oxygen species;    ischemia reperfusion;    interplay between metabolism;    epigenetics;    Mouse;   

DOI  :  10.7554/eLife.60311

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY