Circular RNAs in the pathogenesis of atherosclerosis

Cao, Qidong; Guo, Ziyuan; Du, Shuangshuang; Ling, Hao; Song, Chunli

doi:10.1016/j.lfs.2020.117837

Cited by 83 publications

(32 citation statements)

References 95 publications

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“…Numerous studies provide strong evidence that circRNAs play a critical role in the occurrence and development of atherosclerosis [39][40][41]. Abnormal circRNA expression has been shown to be closely associated with atherosclerosis progression [42,43].…”

Section: Discussionmentioning

confidence: 99%

A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression

et al. 2021

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Atherosclerosis is a fatal disorder that is fundamental to various cardiovascular diseases and severely threatens people's health worldwide. Several studies have demonstrated the role of circular RNAs (circRNAs) in the pathogenesis of atherosclerosis. circUSP36 acts as a key modulator in the progression of atherosclerosis, but the molecular mechanism underlying this role is as yet unclear. This study aimed to elucidate the mechanism by which circUSP36 exerts its function in an in vitro cell model of endothelial cell dysfunction, which is one of pathological features of atherosclerosis. The circRNA traits of circUSP36 were confirmed, and we observed high expression of circUSP36 in endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL). Functional assays revealed that overexpression of circUSP36 suppressed proliferation and migration of ox-LDL-treated endothelial cells. In terms of its mechanism, circUSP36 adsorbed miR-637 by acting as an miRNA sponge. Moreover, enhanced expression of miR-637 abated the impact of circUSP36 on ox-LDL-treated endothelial cell dysregulation. Subsequently, the targeting relationship between miR-637 and WNT4 was predicted using bioinformatics tools and was confirmed via luciferase reporter and RNA pull-down assays. Notably, depletion of WNT4 rescued circUSP36-mediated inhibition of endothelial cell proliferation and migration. In conclusion, circUSP36 regulated WNT4 to aggravate endothelial cell injury caused by ox-LDL by competitively binding to miR-637; this finding indicates circUSP36 to be a promising biomarker for the diagnosis and therapy of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression

et al. 2021

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“…Non-coding RNA (ncRNA) include microRNA (miRNA), long non-coding RNA (lncRNA) as well as circular RNA (circRNA) ( 152 ). ncRNA can regulate the occurrence and development of AS by interacting with proteins, DNA and RNA ( 153 ).…”

Section: Current Perspectives and Limitationsmentioning

confidence: 99%

Metformin, Macrophage Dysfunction and Atherosclerosis

Feng

Chen

et al. 2021

Front. Immunol.

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Metformin is one of the most widely prescribed hypoglycemic drugs and has the potential to treat many diseases. More and more evidence shows that metformin can regulate the function of macrophages in atherosclerosis, including reducing the differentiation of monocytes and inhibiting the inflammation, oxidative stress, polarization, foam cell formation and apoptosis of macrophages. The mechanisms by which metformin regulates the function of macrophages include AMPK, AMPK independent targets, NF-κB, ABCG5/8, Sirt1, FOXO1/FABP4 and HMGB1. On the basis of summarizing these studies, we further discussed the future research directions of metformin: single-cell RNA sequencing, neutrophil extracellular traps (NETs), epigenetic modification, and metformin-based combination drugs. In short, macrophages play an important role in a variety of diseases, and improving macrophage dysfunction may be an important mechanism for metformin to expand its pleiotropic pharmacological profile. In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1β inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging.

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“…Many molecules and mechanisms, such as circRNAs and ceRNAs, are involved in the process of pyroptosis [21,22]. CircRNAs are a type of noncoding RNA that has been reported to mediate different biological and pathological processes, including vascular diseases [23,24]. However, their functions in the progression of vascular cell pyroptosis and roles in atherosclerosis remain to be clearly de ned.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-DAPK1 promotes vascular cell pyroptosis in diabetes by regulating the circ-DAPK1/miR-4454/TXNIP axis.

Chen

Zheng

et al. 2021

Preprint

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Background Circular RNAs have been demonstrated to play an important role in the development of vascular diseases. However, little is known about the role of circ-021774, also named circ-DAPK1, in vascular cell pyroptosis. Methods Circ-DAPK1 was selected from circular RNA sequencing data of HUVECs treated with high glucose medium and normal medium. RT-qPCR was used to determine the expression of circ-DAPK1 in vivo and in vitro. Dual luciferase reporter assay, fluorescence in situ hybridization (FISH) and RNA immunoprecipitation (RIP) were performed to prove the interaction of circ-DAPK1, miRNA-4454 and thioredoxin-interactingprotein (TXNIP). Adeno-associated virus (AAV) was injected intravenously to establish mouse models. PI staining, western-blot and transmission electron microscopy (TEM) analyses were performed to identify the role of circ-DAPK1 in promoting pyroptosis. Results We found that circ-DAPK1 was highly expressed in high glucose medium cultured HUVECs and db/db mice. In vitro and in vivo experiments demonstrated that circ-DAPK1 knockdown decreased the number of PI+ cells, the expression of ASC, NLRP3, GSDMD-N, cleaved caspase-1, IL-18 and IL-1β. In a mechanistic study, the circ-DAPK1/miRNA-4454/TXNIP signaling axis was demonstrated to promote vascular cell pyroptosis in diabetes. Conclusions Circ-DAPK1 functions as a promoter of vascular cell pyroptosis in diabetes via the circ-DAPK1/miRNA-4454/TXNIP signaling axis.

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Circular RNAs in the pathogenesis of atherosclerosis

Cited by 83 publications

References 95 publications

A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression

A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression

Metformin, Macrophage Dysfunction and Atherosclerosis

CircRNA-DAPK1 promotes vascular cell pyroptosis in diabetes by regulating the circ-DAPK1/miR-4454/TXNIP axis.

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