ICMC (Integrated Cardio Metabolic Centre), Myocardial Genetics, Karolinska Institutet, Novum, Hiss A, Våning 7, Hälsovägen 7-9, 141 57 Huddinge, Sweden.
Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden.
Int J Mol Sci. 2020 Nov 27;21(23):9010. doi: 10.3390/ijms21239010.
Epigenetics refers to changes in phenotypes without changes in genotypes. These changes take place in a number of ways, including via genomic DNA methylation, DNA interacting proteins, and microRNAs. The epigenome is the second dimension of the genome and it contains key information that is specific to every type of cell. Epigenetics is essential for many fundamental processes in biology, but its importance in the development and progression of heart failure, which is one of the major causes of morbidity and mortality worldwide, remains unclear. Our understanding of the underlying molecular mechanisms is incomplete. While epigenetics is one of the most innovative research areas in modern biology and medicine, compounds that directly target the epigenome, such as epidrugs, have not been well translated into therapies. This paper focuses on epigenetics in terms of genomic DNA methylation, such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications. These appear to be more dynamic than previously anticipated and may underlie a wide variety of conditions, including heart failure. We also outline possible new strategies for the development of novel therapies.
表观遗传学是指表型的变化而基因型不变。这些变化有多种方式,包括基因组 DNA 甲基化、DNA 相互作用蛋白和 microRNAs。表观基因组是基因组的第二个维度,它包含特定于每种细胞的关键信息。表观遗传学在生物学的许多基本过程中至关重要,但它在心力衰竭(世界范围内发病率和死亡率的主要原因之一)的发展和进展中的重要性尚不清楚。我们对潜在分子机制的理解还不完整。虽然表观遗传学是现代生物学和医学中最具创新性的研究领域之一,但直接针对表观基因组的化合物,如表观遗传药物,尚未很好地转化为治疗方法。本文主要关注基因组 DNA 甲基化,如 5-甲基胞嘧啶 (5mC) 和 5-羟甲基胞嘧啶 (5hmC) 修饰。这些修饰似乎比以前预期的更具动态性,可能是多种情况的基础,包括心力衰竭。我们还概述了开发新型治疗方法的可能的新策略。