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心血管表观遗传学:从 DNA 甲基化到 microRNAs。

Cardiovascular epigenetics: from DNA methylation to microRNAs.

机构信息

Department of Medicine, University of Verona School of Medicine, Verona, Italy.

出版信息

Mol Aspects Med. 2013 Jul-Aug;34(4):883-901. doi: 10.1016/j.mam.2012.08.001. Epub 2012 Sep 6.

Abstract

Epigenetic phenomena are defined as heritable mechanisms that establish and maintain mitotically stable patterns of gene expression without modifying the base sequence of DNA. The major epigenetic features of mammalian cells include DNA methylation, post-translational histone modifications and RNA-based mechanisms including those controlled by small non-coding RNAs (miRNAs). The impact of epigenetic mechanisms in cardiovascular pathophysiology is now emerging as a major player in the interface between genotype to phenotype variability. This topic of research has strict implications on disease development and progression, and opens up possible novel preventive strategies in cardiovascular disease. An important aspect of epigenetic mechanisms is that they are potentially reversible and may be influenced by nutritional-environmental factors and through gene-environment interactions, all of which have an important role in complex, multifactorial diseases such as those affecting the cardiovascular system. Gene expression regulation through the interplay of DNA methylation and histone modifications is well-established, although the knowledge about the function of epigenetic signatures in cardiovascular disease is still largely unexplored. The study of epigenetic markers is, therefore, a very promising frontier of science which may aid in a deeper understanding of molecular mechanisms underlying the modulation of gene expression in the biomolecule pathways linked to cardiovascular diseases. This review focuses on up-to-date knowledge pertaining to the role of epigenetics, from DNA methylation to miRNAs, in major cardiovascular diseases such as ischemic heart disease, hypertension, heart failure and stroke.

摘要

表观遗传现象被定义为可遗传的机制,它在不改变 DNA 碱基序列的情况下建立和维持有丝分裂稳定的基因表达模式。哺乳动物细胞的主要表观遗传特征包括 DNA 甲基化、组蛋白翻译后修饰以及基于 RNA 的机制,包括由小非编码 RNA(miRNA)控制的机制。表观遗传机制在心血管病理生理学中的作用现在正成为基因型到表型变异性之间界面的主要参与者。这一研究主题对疾病的发展和进展有严格的影响,并为心血管疾病开辟了可能的新的预防策略。表观遗传机制的一个重要方面是它们具有潜在的可逆转性,可能受到营养-环境因素和基因-环境相互作用的影响,所有这些因素在复杂的多因素疾病中都起着重要作用,如影响心血管系统的疾病。DNA 甲基化和组蛋白修饰相互作用的基因表达调控是众所周知的,尽管关于表观遗传特征在心血管疾病中的功能的知识在很大程度上仍未被探索。因此,研究表观遗传标记是一个非常有前途的科学前沿,它可能有助于更深入地了解与心血管疾病相关的生物分子途径中基因表达调控的分子机制。这篇综述重点介绍了从 DNA 甲基化到 miRNA 的表观遗传学在缺血性心脏病、高血压、心力衰竭和中风等主要心血管疾病中的最新知识。

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