Garratt Hester, Ashburn Robert, Sopić Miron, Nogara Antonella, Caporali Andrea, Mitić Tijana
Centre for Cardiovascular Science, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
Noncoding RNA. 2021 Sep 23;7(4):62. doi: 10.3390/ncrna7040062.
The vascular endothelium comprises the interface between the circulation and the vessel wall and, as such, is under the dynamic regulation of vascular signalling, nutrients, and hypoxia. Understanding the molecular drivers behind endothelial cell (EC) and vascular smooth muscle cell (VSMC) function and dysfunction remains a pivotal task for further clinical progress in tackling vascular disease. A newly emerging era in vascular biology with landmark deep sequencing approaches has provided us with the means to profile diverse layers of transcriptional regulation at a single cell, chromatin, and epigenetic level. This review describes the roles of major vascular long non-coding RNA (lncRNAs) in the epigenetic regulation of EC and VSMC function and discusses the recent progress in their discovery, detection, and functional characterisation. We summarise new findings regarding lncRNA-mediated epigenetic mechanisms-often regulated by hypoxia-within the vascular endothelium and smooth muscle to control vascular homeostasis in health and disease. Furthermore, we outline novel molecular techniques being used in the field to delineate the lncRNA subcellular localisation and interaction with proteins to unravel their biological roles in the epigenetic regulation of vascular genes.
血管内皮构成了循环系统与血管壁之间的界面,因此处于血管信号传导、营养物质和缺氧的动态调节之下。了解内皮细胞(EC)和血管平滑肌细胞(VSMC)功能及功能障碍背后的分子驱动因素,仍然是在攻克血管疾病方面取得进一步临床进展的关键任务。血管生物学中一个具有里程碑意义的深度测序方法的新兴时代,为我们提供了在单细胞、染色质和表观遗传水平上剖析转录调控不同层面的手段。本综述描述了主要血管长链非编码RNA(lncRNA)在EC和VSMC功能的表观遗传调控中的作用,并讨论了它们在发现、检测和功能表征方面的最新进展。我们总结了关于lncRNA介导的表观遗传机制(通常受缺氧调节)在血管内皮和平滑肌内控制健康和疾病状态下血管稳态的新发现。此外,我们概述了该领域正在使用的新型分子技术,以描绘lncRNA的亚细胞定位及其与蛋白质的相互作用,从而揭示它们在血管基因表观遗传调控中的生物学作用。