Noncoding RNAs regulate NF-κB signaling to modulate blood vessel inflammation

Abstract

Cardiovascular diseases such as atherosclerosis are one of the leading causes of morbidity and mortality worldwide. The clinical manifestations of atherosclerosis, which include heart attack and stroke, occur several decades after initiation of the disease and become more severe with age. Inflammation of blood vessels plays a prominent role in atherogenesis. Activation of the endothelium by inflammatory mediators leads to the recruitment of circulating inflammatory cells, which drives atherosclerotic plaque formation and progression. Inflammatory signaling within the endothelium is driven predominantly by the pro-inflammatory transcription factor, NF-κB. Interestingly, activation of NF-κB is enhanced during the normal aging process and this may contribute to the development of cardiovascular disease. Importantly, studies utilizing mouse models of vascular inflammation and atherosclerosis are uncovering a network of noncoding RNAs, particularly microRNAs, which impinge on the NF-κB signaling pathway. Here we summarize the literature regarding the control of vascular inflammation by microRNAs, and provide insight into how these microRNA-based pathways might be harnessed for therapeutic treatment of disease. We also discuss emerging areas of endothelial cell biology, including the involvement of long noncoding RNAs and circulating microRNAs in the control of vascular inflammation.

miR-155 Modifies Inflammation, Endothelial Activation and Blood-Brain Barrier Dysfunction in Cerebral Malaria

“…In this study, genetic disruption of miR-155 was associated with increased circulating levels of proinflammatory cytokines and increased parasitemia during PbA infection. Conflicting roles for miR-155 in inflammation have been described (50). miR-155 has been shown to target suppressor of cytokine signaling 1, thereby modulating IFN-γ signaling, but this miRNA has also been proposed to genes at distal sites (39,40).…”

CXCL16 in Vascular Pathology Research: from Macro Effects to microRNAs

“…Cardiovascular diseases are among them. Because there are already thorough reviews that summarize current knowledge about miRs implicated in atherosclerosis susceptibility, development, and progression [81][82][83][84][85][86][87][88] , we will focus on the part of atherosclerosis pathology where different miRs could potentially alter vascular physiology by the direct or indirect regulation of CXCL16 gene expression.…”

ApoE Attenuates Atherosclerosis via miR-146a

“…Mice deficient in miR-146a have prolonged T-cell responses, excessive and lethal responses to endotoxin and develop autoimmunity and tumors. 18 These phenotypes are invariably associated with enhanced and prolonged NF-κB-dependent responses.…”

“…In the case of miR-146a, multiple components of proinflammatory signaling pathways (including TRAF6, IRAK1, IRAK2, MyD88, RelB, STAT1, CARD10, and TLR4) have been identified as bona fide targets. 18 Deletion of miR-146a in mice has revealed that this microRNA dampens and extinguishes inflammatory signaling cascades. Mice deficient in miR-146a have prolonged T-cell responses, excessive and lethal responses to endotoxin and develop autoimmunity and tumors.…”

“…These include proteins that antagonize the NF-κB signaling pathway, such as IκBα and A20, as well as several microRNAs, most prominently, miR-146a. 18 MicroRNAs bind primarily to the 3′ untranslated regions of target mRNAs and suppress protein production. In the case of miR-146a, multiple components of proinflammatory signaling pathways (including TRAF6, IRAK1, IRAK2, MyD88, RelB, STAT1, CARD10, and TLR4) have been identified as bona fide targets.…”