Genetics and epigenetics of arrhythmia and heart failure.
Genetics and epigenetics of arrhythmia and heart failure.
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DOI：
10.3389/fgene.2013.00219
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发表时间：
2013-10-30
影响因子：
3.7
通讯作者：
da Costa Martins PA
中科院分区：
文献类型：
--
作者：
Duygu B;Poels EM;da Costa Martins PA
心力衰竭（HF）是包括心肌梗死、心脏肥大和高血压在内的几种病理性心脏疾病的终末期。各种分子和细胞机制参与HF的发展。在分子水平上，HF的发生与基因表达的重编程有关，包括α-肌球蛋白重链（α-MHC）基因和肌浆网Ca 2+ ATP酶基因的下调以及胎儿心脏特异性基因如心房利钠因子和脑利钠肽的重新激活。基因表达的这些偏差导致结构和电生理变化，最终进展为HF。心律失常是由心脏的传导特性改变引起的，这可能是由于局部缺血、炎症、纤维化、衰老或遗传因素引起的。由于基因转录程序的变化可能会导致心脏功能恶化，因此了解该过程中涉及的分子机制已成为该领域的优先事项。在这种情况下，各种研究除了确定HF患者中不同的DNA甲基化模式外，还关注特定的疾病过程及其潜在机制，还引入了表观基因组学等新概念。本文重点介绍了与HF发病和进展相关的特定基因突变，并介绍了表观遗传学机制，如组蛋白修饰，DNA甲基化和基于RNA的修饰，并强调了表观遗传学，胚胎发生和HF之间的关系。
Heart failure (HF) is the end stage of several pathological cardiac conditions including myocardial infarction, cardiac hypertrophy and hypertension. Various molecular and cellular mechanisms are involved in the development of HF. At the molecular level, the onset of HF is associated with reprogramming of gene expression, including downregulation of the alpha-myosin heavy chain (α-MHC) gene and sarcoplasmic reticulum Ca 2+ ATPase genes and reactivation of specific fetal cardiac genes such as atrial natriuretic factor and brain natriuretic peptide. These deviations in gene expression result in structural and electrophysiological changes, which eventually progress to HF. Cardiac arrhythmia is caused by altered conduction properties of the heart, which may arise in response to ischemia, inflammation, fibrosis, aging or from genetic factors. Because changes in the gene transcription program may have crucial consequences as deteriorated cardiac function, understanding the molecular mechanisms involved in the process has become a priority in the field. In this context, various studies besides having identified different DNA methylation patterns in HF patients, have also focused on specific disease processes and their underlying mechanisms, also introducing new concepts such as epigenomics. This review highlights specific genetic mutations associated with the onset and progression of HF, also providing an introduction to epigenetic mechanisms such as histone modifications, DNA methylation and RNA-based modification, and highlights the relation between epigenetics, arrhythmogenesis and HF.