Epigenetic regulation in heart failure.
Epigenetic regulation in heart failure.
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DOI：
10.1097/hco.0000000000000276
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发表时间：
2016-05
影响因子：
2.3
通讯作者：
Hill JA
中科院分区：
文献类型：
--
作者：
Kim SY;Morales CR;Gillette TG;Hill JA
概述基因调控的主要机制及其与心力衰竭病理生理的相关性，并重点介绍最新发现。心衰综合征是一种复杂且非常普遍的疾病，其中心脏经历了大量的结构重塑。心衰的病理生理是由多种疾病相关的线索触发的，由遗传和表观遗传事件共同控制。表观遗传机制，如染色质/DNA修饰和非编码rna，已经成为控制基因表达的环境刺激的分子转导器。在这里，我们强调代谢环境，衰老和血流动力学应激，因为它们影响心肌的表观遗传景观。最近在多个领域的研究，包括癌症、干细胞、发育和心血管生物学，已经发现了表观遗传机制、细胞能量学和线粒体功能之间的生化联系。阐明这些联系将为长期建立的流行病学观察提供分子见解。随着时间的推移，利用表观遗传机制进行治疗可能具有临床意义。
To provide an overview, highlighting recent findings, of a major mechanism of gene regulation and its relevance to the pathophysiology of heart failure. The syndrome of heart failure is a complex and highly prevalent condition, one in which the heart undergoes substantial structural remodeling. Triggered by a wide range of disease-related cues, heart failure pathophysiology is governed by both genetic and epigenetic events. Epigenetic mechanisms, such as chromatin/DNA modifications and non-coding RNAs, have emerged as molecular transducers of environmental stimuli to control gene expression. Here, we emphasize metabolic milieu, aging, and hemodynamic stress as they impact the epigenetic landscape of the myocardium. Recent studies in multiple fields, including cancer, stem cells, development, and cardiovascular biology, have uncovered biochemical ties linking epigenetic machinery and cellular energetics and mitochondrial function. Elucidation of these connections will afford molecular insights into long-established epidemiological observations. With time, exploitation of the epigenetic machinery therapeutically may emerge with clinical relevance.