Metabolic substrates, histone modifications, and heart failure.

Zihang Huang, Shuai Song, Xiaokai Zhang, Linqi Zeng, Aijun Sun, Junbo Ge

Journal: Biochimica et biophysica acta. Gene regulatory mechanisms 2023;1866(1):194898

PMID: 36403753

Full Text on Elsevier Science View on PubMed

Abstract

Histone epigenetic modifications are chemical modification changes to histone amino acid residues that modulate gene expression without altering the DNA sequence. As both the phenotypic and causal factors, cardiac metabolism disorder exacerbates mitochondrial ATP generation deficiency, thus promoting pathological cardiac hypertrophy. Moreover, several concomitant metabolic substrates also promote the expression of hypertrophy-responsive genes via regulating histone modifications as substrates or enzyme-modifiers, indicating their dual roles as metabolic and epigenetic regulators. This review focuses on the cardiac acetyl-CoA-dependent histone acetylation, NAD-dependent SIRT-mediated deacetylation, FAD-dependent LSD-mediated, and α-KG-dependent JMJD-mediated demethylation after briefly addressing the pathological and physiological cardiac energy metabolism. Besides using an "iceberg model" to explain the dual role of metabolic substrates as both metabolic and epigenetic regulators, we also put forward that the therapeutic supplementation of metabolic substrates is promising to blunt HF via re-establishing histone modifications.

Address: Department of Cardiology, Zhongshan Hospital, Fudan University, China; Shanghai Institute of Cardiovascular Diseases, Shanghai, China.; Department of Cardiology, Zhongshan Hospital, Fudan University, China; Shanghai Institute of Cardiovascular Diseases, Shanghai, China; Institute of Biomedical Sciences, Fudan University, Shanghai, China; National Clinical Research for Interventional Medicine, China. Electronic address: [email protected].; Department of Cardiology, Zhongshan Hospital, Fudan University, China; Shanghai Institute of Cardiovascular Diseases, Shanghai, China; Institute of Biomedical Sciences, Fudan University, Shanghai, China; National Clinical Research for Interventional Medicine, China.

DOI: 10.1016/j.bbagrm.2022.194898