Abstract
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.
Highlights
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
The vascular endothelium comprises the layer of endothelial cells (ECs) that create the interface between the circulation and the vessel wall that is under dynamic regulation in accordance with its environment to maintain perfusion and the supply of oxygen and nutrients required for cellular metabolism [1,2]
Expressed gene 3 (MEG3) is a major hypoxia-sensitive long non-coding RNAs (lncRNAs) which interacts with polycomb repressive complex 2 (PRC2) and has complex roles in EC function
Summary
The vascular endothelium comprises the layer of endothelial cells (ECs) that create the interface between the circulation and the vessel wall that is under dynamic regulation in accordance with its environment to maintain perfusion and the supply of oxygen and nutrients required for cellular metabolism [1,2]. Endothelial cell dysfunction can occur due to hypoxic or oxidative injury and predisposes to atherosclerotic and ischaemic disease by potentiating vascular inflammation and atherothrombosis (Figure 1B). B) Upstream arterial stenosis or occlusion due to atherosclerosis may result in ischaemia cells. The large number of nonsequences, introns, and interspersed nuclear elements. RNAs named short (microRNA, miRNA) and long non-coding RNAs (lncRNAs) reguregulate important cellular functions—including within vascular the ENlate important cellular functions—including within vascular cells.
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