Department of Cardiology, National University Heart Centre, Singapore 119228, Singapore.
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Int J Mol Sci. 2024 Nov 8;25(22):12010. doi: 10.3390/ijms252212010.
Heart failure is a clinical syndrome with rising global incidence and poor prognosis despite improvements in medical therapy. There is increasing research interest in epigenetic therapies for heart failure. Pathological cardiac remodelling may be driven by stress-activated cardiac signalling cascades, and emerging research has shown the involvement of epigenetic signals that regulate transcriptional changes leading to heart failure. In this review, we appraise the current evidence for the role of epigenetic modifications in heart failure. These include DNA methylation and histone modifications by methylation, acetylation, phosphorylation, ubiquitination and sumoylation, which are critical processes that establish an epigenetic pattern and translate environmental stress into genetic expression, leading to cardiac remodeling. We summarize the potential epigenetic therapies currently in development, including the limited clinical trials of epigenetic therapies in heart failure. The dynamic changes in the epigenome in the disease process require further elucidation, and so does the impact of this process on the development of therapeutics. Understanding the role of epigenetics in heart failure may pave the way for the identification of novel biomarkers and molecular targets, and facilitate the development of personalized therapies for this important condition.
心力衰竭是一种临床综合征，尽管医学治疗有所改善，但全球发病率和预后仍较差。尽管医学治疗有所改善，但心力衰竭的表观遗传学治疗方法越来越受到关注。病理性心脏重构可能是由应激激活的心脏信号级联驱动的，新出现的研究表明，表观遗传信号参与了调节导致心力衰竭的转录变化。在这篇综述中，我们评估了表观遗传修饰在心力衰竭中的作用的现有证据。这些包括 DNA 甲基化和通过甲基化、乙酰化、磷酸化、泛素化和 sumoylation 进行的组蛋白修饰，这些都是建立表观遗传模式并将环境应激转化为遗传表达，导致心脏重构的关键过程。我们总结了目前正在开发的潜在表观遗传疗法，包括心力衰竭中表观遗传疗法的有限临床试验。疾病过程中表观基因组的动态变化需要进一步阐明，这一过程对治疗发展的影响也是如此。了解表观遗传学在心力衰竭中的作用可能为识别新的生物标志物和分子靶点铺平道路，并为这一重要疾病的个体化治疗提供便利。
