Department of Clinical & Translational Research, Western University of Health Sciences, Pomona, CA, USA.
Adv Exp Med Biol. 2020;1229:133-148. doi: 10.1007/978-981-15-1671-9_7.
Epigenetic gene regulations can be considered as de-novo initiation of abnormal molecular signaling events whose regulation is otherwise required during normal or specific developmental stages of the organisms. Primarily, three different mechanisms have been identified to participate in epigenetic gene regulations which include, DNA methylation, non-coding RNA species (microRNAs [miRNA], and long non-coding RNAs [LNC-RNA]) and histone modifications. These de-novo epigenetic mechanisms have been associated with altered normal cellular functions which eventually facilitate normal cells to transition into an abnormal phenotype. Among the three modes of regulation, RNA species which are usually considered to be less stable, can be speculated to initiate instant alterations in gene expression compared to DNA methylation or histone modifications. However, LNC-RNAs appear to be more stable in the cells than the other RNA species. Moreover, there is increasing literature which clearly suggests that a single specific LNC-RNA can regulate multiple mechanisms and disease phenotypes. With specific focus on cardiovascular diseases, here we attempt to provide UpToDate information on the functional role of miRNAs and LNC-RNAs. Here we discuss the role of these epigenetic mediators in different components of cardiovascular disease which include physiopathological heart development, athersclerosis, retenosis, diabetic hearts, myocardial infarction, ischemia-reperfusion, heart valve disease, aortic aneurysm, osteogenesis, angiogenesis and hypoxia in the heart. While there is abundant literature support that shows the involvement of many LNC-RNAs and miRNAs in cardiovascular diseases, very few RNA species have been identified which regulate epigenetic mechanisms which is the current focus in this article. Understanding the role of these RNA species in regulating epigenetic mechanisms in different cell types causing cardiovascular disease, would advance the field and promote disease prevention approaches that are aimed to target epigenetic mechanisms.
表观遗传基因调控可被视为异常分子信号事件的从头开始,这些调控在生物体的正常或特定发育阶段是必需的。主要有三种不同的机制被确定参与表观遗传基因调控,包括 DNA 甲基化、非编码 RNA 种类(microRNAs [miRNA] 和长非编码 RNA [LNC-RNA])和组蛋白修饰。这些从头发生的表观遗传机制与改变正常细胞功能有关,最终使正常细胞向异常表型转化。在这三种调控模式中,通常被认为不太稳定的 RNA 种类可以推测比 DNA 甲基化或组蛋白修饰更快地引发基因表达的瞬时改变。然而,LNC-RNAs 在细胞中的稳定性似乎比其他 RNA 种类更高。此外,越来越多的文献清楚地表明,单个特定的 LNC-RNA 可以调节多种机制和疾病表型。本文特别关注心血管疾病,试图提供有关 miRNA 和 LNC-RNAs 功能作用的 UpToDate 信息。在这里,我们讨论了这些表观遗传介质在心血管疾病的不同组成部分中的作用,包括生理病理性心脏发育、动脉粥样硬化、再狭窄、糖尿病心脏、心肌梗死、缺血再灌注、心脏瓣膜病、主动脉瘤、成骨、血管生成和心脏缺氧。虽然有大量文献表明许多 LNC-RNAs 和 miRNA 参与心血管疾病,但只有少数 RNA 种类被确定调节表观遗传机制,这是本文的当前重点。了解这些 RNA 种类在调节不同细胞类型中引起心血管疾病的表观遗传机制中的作用,将推进该领域的发展,并促进旨在靶向表观遗传机制的疾病预防方法。