期刊
JACC-BASIC TO TRANSLATIONAL SCIENCE
卷 7, 期 4, 页码 348-362出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2021.12.007
关键词
acetylation of H3K9; cardiomyopathy; enoyl-CoA hydratase 1; nicotinamide mononucleotide; p300
资金
- Key Development Programs of Basic Research of China [2020YFA0803601, 2019YFA0801900, SQ2018YFC100242]
- National Natural Science Foundation of China [81771627, 31871432, 81971061, 81770312, 82170305, 81873481]
ECHS1 deficiency causes cardiac dysfunction through promoting p300 nuclear translocation and increasing H3K9 acetylation. Targeting acetylation can alleviate the cardiomyopathy phenotypes induced by ECHS1 deficiency.
Short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency plays a rote in cardiomyopathy. Whether ECHS1 deficiency causes or is only associated with cardiomyopathy remains unclear. By using Echs1 heterogeneous knockout (Echsr(+/-)) mice, we found that ECHS1 deficiency caused cardiac dysfunction, as evidenced by diffuse myocardial fibrosis and upregulated fibrosis-related genes. Mechanistically, ECHS1 interacts with the p300 nuclear localization sequence, preventing its nuclear translocation in fibroblasts. ECHS1 deficiency promotes p300 nuclear translocation, leading to increased H3K9 acetylation, a known risk factor for cardiomyopathy. Nicotinamide mononucleotide-mediated acetylation targeting suppressed ECHS1 deficiency-induced cardiomyopathy phenotypes in Echs1(+/-) mice. Thus, enhancing p300-mediated H3K9ac is a potential interventional approach for preventing ECHS1 deficiency-induced cardiomyopathy. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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