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长链非编码 RNA 与血管生物学和疾病

LncRNAs in vascular biology and disease.

机构信息

Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Vascul Pharmacol. 2019 Mar;114:145-156. doi: 10.1016/j.vph.2018.01.003. Epub 2018 Feb 6.

Abstract

Accumulating studies indicate that long non-coding RNAs (lncRNAs) play important roles in the regulation of diverse biological processes involved in homeostatic control of the vessel wall in health and disease. However, our knowledge of the mechanisms by which lncRNAs control gene expression and cell signaling pathways is still nascent. Furthermore, only a handful of lncRNAs has been functionally evaluated in response to pathophysiological stimuli or in vascular disease states. For example, lncRNAs may regulate endothelial dysfunction by modulating endothelial cell proliferation (e.g. MALAT1, H19) or angiogenesis (e.g. MEG3, MANTIS). LncRNAs have also been implicated in modulating vascular smooth muscle cell (VSMC) phenotypes or vascular remodeling (e.g. ANRIL, SMILR, SENCR, MYOSLID). Finally, emerging studies have implicated lncRNAs in leukocytes activation (e.g. lincRNA-Cox2, linc00305, THRIL), macrophage polarization (e.g. GAS5), and cholesterol metabolism (e.g. LeXis). This review summarizes recent findings on the expression, mechanism, and function of lncRNAs implicated in a range of vascular disease states from mice to human subjects. An improved understanding of lncRNAs in vascular disease may provide new pathophysiological insights and opportunities for the generation of a new class of RNA-based biomarkers and therapeutic targets.

摘要

越来越多的研究表明,长非编码 RNA(lncRNA)在调节血管壁稳态的多种生物学过程中发挥重要作用,无论是在健康状态还是疾病状态下。然而,我们对于 lncRNA 如何控制基因表达和细胞信号通路的机制的了解还处于起步阶段。此外,只有少数 lncRNA 已经在针对病理生理刺激或血管疾病状态的功能评估中得到了研究。例如,lncRNA 可以通过调节内皮细胞增殖(如 MALAT1、H19)或血管生成(如 MEG3、MANTIS)来调节内皮功能障碍。lncRNA 还被认为在调节血管平滑肌细胞(VSMC)表型或血管重塑(如 ANRIL、SMILR、SENCR、MYOSLID)中发挥作用。最后,新出现的研究表明,lncRNA 参与了白细胞激活(如 lincRNA-Cox2、linc00305、THRIL)、巨噬细胞极化(如 GAS5)和胆固醇代谢(如 LeXis)。本文综述了最近在从小鼠到人类的一系列血管疾病状态中,与 lncRNA 相关的表达、机制和功能的研究发现。对血管疾病中 lncRNA 的深入了解可能为新的 RNA 类生物标志物和治疗靶点的产生提供新的病理生理学见解和机会。

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