Long Non-Coding RNAs in Vascular Inflammation

Abstract

Less than 2% of the genome encodes for proteins. Accumulating studies have revealed a diverse set of RNAs derived from the non-coding genome. Among them, long non-coding RNAs (lncRNAs) have garnered widespread attention over recent years as emerging regulators of diverse biological processes including in cardiovascular disease (CVD). However, our knowledge of their mechanisms by which they control CVD-related gene expression and cell signaling pathways is still limited. Furthermore, only a handful of lncRNAs has been functionally evaluated in the context of vascular inflammation, an important process that underlies both acute and chronic disease states. Because some lncRNAs may be expressed in cell- and tissue-specific expression patterns, these non-coding RNAs hold great promise as novel biomarkers and as therapeutic targets in health and disease. Herein, we review those lncRNAs implicated in pro- and anti-inflammatory processes of acute and chronic vascular inflammation. An improved understanding of lncRNAs in vascular inflammation may provide new pathophysiological insights in CVD and opportunities for the generation of a new class of RNA-based biomarkers and therapeutic targets.

LncRNA VINAS regulates atherosclerosis by modulating NF-κB and MAPK signaling

“…Arterial inflammation occurs very early in atherogenesis and is associated with impairment of many salutary functions of the healthy endothelium. Accumulating studies point to lncRNAs as regulators of endothelial homeostasis, smooth muscle cell contractility, and macrophage-mediated inflammation in the vessel wall (11,13,(15)(16)(17)(18). This study provides evidence for the first time to our knowledge that the mouse-specific lncRNA VINAS and its human ortholog, DEPDC4, play important roles in vascular inflammation and atherogenesis.…”

“…Recently, long noncoding RNAs (lncRNAs) have emerged as powerful regulators of nearly all biological processes by exerting epigenetic, transcriptional, or translational control of target genes owing to their polyvalent binding properties to RNA, DNA, and protein as well as acting as molecular sponges for other transcripts and miRNAs (11,12). However, the role of lncRNAs in vascular inflammation and cardiovascular diseases is just now emerging (13). Identification of lncRNAs specifically expressed in the Long noncoding RNAs (lncRNAs) play important roles in regulating diverse cellular processes in the vessel wall, including atherosclerosis.…”

Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition

“…Moreover, our results exhibited the increased levels of COX-2, NO, IL-1β, IL-6, TNF-α, MDA, cleaved caspase-3, NOX4, iNOS and p47phox whereas reduced levels of SOD, collagen I, and collagen III further support our hypothesis. Additionally, LncRNA RP5-833A20.1 has also been reported to elevate the levels of inflammatory factors, such as IL-1β, IL-6, and, TNF-α in THP-1 macrophages in cardiovascular disease [ 23 ]. Besides, inhibition of lncRNA HIF 1 alpha-antisense RNA 1 (HIF1α-AS1) by siRNA can suppress the apoptosis and promote the proliferation of VSMCs by decreasing the caspase-3 expression in thoracic aortic aneurysms [ 24 ].…”

LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

“…These activated transcription factors, in turn, stimulate the expression of proinflammatory cytokines, chemokines, interferons and other pro-inflammatory mediators, and thus propagating cellular inflammation 27 – 29 . Emerging evidences suggest that, in addition to proteins, noncoding RNAs (ncRNA) play critical roles in variety of cell signaling process including in regulation of gene expression and immune response 30 – 32 . NcRNAs are recently discovered class of transcripts that coded by the genome, but mostly remain untranslated into proteins 33 – 35 .…”