期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1866, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbagrm.2022.194898
关键词
Epigenetics; Histone acetylation; Histone methylation; Heart failure; Metabolic substrates
This review summarizes the impact of cardiac metabolism disorder on histone modifications and gene expression, as well as the dual role of metabolic substrates in regulating cardiac hypertrophy. The article suggests the therapeutic supplementation of metabolic substrates as a potential approach to restore histone modifications.
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 alpha-KG-depen-dent 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.
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