The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling

Mahmoud, Amira D.; Ballantyne, Margaret D.; Miscianinov, Vladislav; Pinel, Karine; Hung, John; Scanlon, Jessica P.; Iyinikkel, Jean; Kaczynski, Jakub; Tavares, Adriana; Bradshaw, Angela C.; Mills, Nicholas L; Newby, David E.; Caporali, Andrea; Gould, Gwyn W.; George, Sarah J.; Ulitsky, Igor; Sluimer, Judith C.; Rodor, Julie; Baker, Andrew H.

doi:10.1161/circresaha.119.314876

Cited by 117 publications

(118 citation statements)

References 54 publications

(69 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 63%

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

Simion¹,

Zhou²,

Pierce³

et al. 2020

JCI Insight

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Section: Discussionmentioning

confidence: 63%

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

Simion¹,

Zhou²,

Pierce³

et al. 2020

JCI Insight

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“…Lee K et al identified 914 DEGs between stable and ruptured plaques by using microarray technology, and highlighted the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture (Lee et al, 2013). Mahmoud AD et al revealed the DEGs between stable and unstable plaques, which were mainly linked with the plaque instability, including inflammation, matrix remodeling, and calcification (Mahmoud et al, 2019). Although these studies revealed some molecular mechanisms of the atherosclerosis development in various aspects, they could not reveal the cell-specific mechanisms, such as foam cells.…”

Section: Discussionmentioning

confidence: 99%

“…GSE41571 (Lee et al, 2013) contains data on 11 macrophage-rich regions from five ruptured plaques and six stable plaques. GSE120521 (Mahmoud et al, 2019) consists of an RNA-seq profile of four stable and four unstable plaque samples. The analysis strategy is shown in Fig.…”

Section: Data Resourcesmentioning

confidence: 99%

Analysis of genes and underlying mechanisms involved in foam cells formation and atherosclerosis development

Zhang

Qin

Zhou

et al. 2020

PeerJ

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Background Foam cells (FCs) play crucial roles in the process of all stages of atherosclerosis. Smooth muscle cells (SMCs) and macrophages are the major sources of FCs. This study aimed to identify the common molecular mechanism in these two types of FCs. Methods GSE28829, GSE43292, GSE68021, and GSE54666 were included to identify the differentially expressed genes (DEGs) associated with FCs derived from SMCs and macrophages. Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the DAVID database. The co-regulated genes associated with the two origins of FCs were validated (GSE9874), and their expression in vulnerable atherosclerosis plaques (GSE120521 and GSE41571) was assessed. Results A total of 432 genes associated with FCs derived from SMCs (SMC-FCs) and 81 genes associated with FCs derived from macrophages (M-FCs) were identified, and they were mainly involved in lipid metabolism, inflammation, cell cycle/apoptosis. Furthermore, three co-regulated genes associated with FCs were identified: GLRX, RNF13, and ABCA1. These three common genes showed an increased tendency in unstable or ruptured plaques, although in some cases, no statistically significant difference was found. Conclusions DEGs related to FCs derived from SMCs and macrophages have contributed to the understanding of the molecular mechanism underlying the formation of FCs and atherosclerosis. GLRX, RNF13, and ABCA1 might be potential targets for atherosclerosis treatment.

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“…Further, lncRNA MIAT were detected to be elevated in the blood of ischemic stroke patients [85]. LncRNA SMILR seems to play a role in plaque stability [58], and its plasma levels positively correlate with C-reactive protein [59]. SNPs in the lncRNA MIAT promoter correlated with acute myocardial infarction in a Chinese Han population [86], while a specific polymorphism in MALAT1 (rs619586AG/GG) might be CVD protective [87].…”

Section: Lncrnas As Biomarkers In Atherosclerosismentioning

confidence: 97%

“…One example for lncRNA-mRNA interaction is lncRNA SMILR (smooth muscle–induced lncRNA). SMILR did directly bind the mRNA of the mitotic protein CENPF (centromere protein F) and promoted the proliferation of VSMCs [ 58 ]. In agreement with VSMC proliferation conferring with plaque stability, increased SMILR levels were detected in unstable compared with stable human atherosclerotic plaques [ 59 ].…”

Section: Lncrna-rna Interactions In Atherosclerosismentioning

confidence: 99%

The Long Non-coding Road to Atherosclerosis

Josefs

Boon

2020

Curr Atheroscler Rep

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Purpose of Review To summarize recent insights into long non-coding RNAs (lncRNAs) involved in atherosclerosis. Because atherosclerosis is the main underlying pathology of cardiovascular diseases (CVD), the world's deadliest disease, finding novel therapeutic strategies is of high interest. Recent Findings LncRNAs can bind to proteins, DNA, and RNA regulating disease initiation and plaque growth as well as plaque stability in different cell types such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages. A number of lncRNAs have been implicated in cholesterol homeostasis and foam cell formation such as LASER, LeXis, and CHROME. Among others, MANTIS, lncRNA-CCL2, and MALAT1 were shown to be involved in vascular inflammation. Further regulations include, but are not limited to, DNA damage response in ECs, phenotypic switch of VSMCs, and various cell death mechanisms. Interestingly, some lncRNAs are closely correlated with response to statin treatment, such as NEXN-AS1 or LASER. Additionally, some lncRNAs may serve as CVD biomarkers. Summary LncRNAs are a potential novel therapeutic target to treat CVD, but research of lncRNA in atherosclerosis is still in its infancy. With increasing knowledge of the complex and diverse regulations of lncRNAs in the heterogeneous environment of atherosclerotic plaques, lncRNAs hold promise for their clinical translation in the near future.

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The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling

Abstract: Supplemental Digital Content is available in the text.

Cited by 117 publications

References 54 publications

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

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

Analysis of genes and underlying mechanisms involved in foam cells formation and atherosclerosis development

The Long Non-coding Road to Atherosclerosis

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