Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation.
Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation.
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作者：
Lei I;Tian S;Gao W;Liu L;Guo Y;Tang P;Chen E;Wang Z
心肌梗死（MI）伴随着严重的能量剥夺和广泛的表观遗传变化。然而，如何在MI和心脏修复过程中能量代谢和染色质修饰相互关联的探索很少。在这里，我们研究了参与乙酰辅酶A合成的主要代谢途径的不同碳源对心肌梗死的影响，发现辛酸钠（8 C）升高乙酰辅酶A显著改善缺血再灌注（I/R）大鼠的心脏功能。在机制上，8 C通过促进组蛋白乙酰化而减少I/R损伤，这反过来激活抗氧化基因的表达并抑制心肌细胞（CM）凋亡。此外，我们阐明了8 C促进的组蛋白乙酰化和心脏修复是通过代谢酶中链酰基辅酶A脱氢酶（MCAD）和组蛋白乙酰转移酶Kat 2a进行的，表明8 C主要通过代谢乙酰辅酶A介导的组蛋白乙酰化显著改善心脏功能。因此，我们的研究揭示了一个相互关联的代谢/表观遗传网络，包括8 C，乙酰辅酶A，MCAD和Kat 2a，以对抗心脏损伤。
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.