Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis

Li, Yanbing; Yang, Geng; Zhou, Boda; Wu, Xuejiao; Zhang, Ou; Guan, Xiaoxu; Liu, Siyuan; Zhuang, Xianjing; Zhou, Jie; Chang, Meng-Wei; Miao, Guobin; Wang, Lizhong

doi:10.1007/s12035-021-02332-x

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…The high expression of miR-20b can inhibit endothelial cell aging, which may be through TXNIP/NLRP3 axis to inhibit Wnt/ β -catenin path implementation [ 71 ]. In addition, a study has confirmed that depleted GAS5 inhibits TXNIP by upregulating miR-194-3p, promotes the growth of vascular ECs, and reduces the formation of atherosclerotic plaque in AS [ 72 ].…”

Section: The Role Of Txnip In Diseasementioning

confidence: 99%

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Pan

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Thioredoxin-interacting protein (TXNIP) was originally named vitamin D3 upregulated protein-1 (VDUP1) because of its ability to bind to thioredoxin (TRX) and inhibit TRX function and expression. TXNIP is an alpha-arrestin protein that is essential for redox homeostasis in the human body. TXNIP may act as a double-edged sword in the cell. The balance of TXNIP is crucial. A study has shown that TXNIP can travel between diverse intracellular locations and bind to different proteins to play different roles under oxidative stress. The primary function of TXNIP is to induce apoptosis or pyroptosis under oxidative stress. TXNIP also inhibits proliferation and migration in cancer cells, although TXNIP levels decrease, and function diminishes in various cancers. In this review, we summarized the main structure, binding proteins, pathways, and the role of TXNIP in diseases, aiming to explore the double-edged sword role of TXNIP, and expect it to be helpful for future treatment using TXNIP as a therapeutic target.

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Section: The Role Of Txnip In Diseasementioning

confidence: 99%

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Pan

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…AAA involves chronic inflammation of blood vessel walls. Thioredoxin-interacting protein (TXNIP) inflammasome-mediated inflammation in macrophages has an important role in various cardiovascular diseases, including AAA and atherosclerosis [ 7 – 9 ]. Usui et al found that TXNIP-NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation by mitochondrial oxidative stress in macrophages leads to the development of AAA, while the inhibition of NLRP3 can inhibit aneurysmal formation, arterial dilation rate, and inflammatory cell infiltration of ApoE −/− mice induced by angiotensin II (Ang II) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Jiang

et al. 2022

Stem Cell Res Ther

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Background Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. Methods ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Results The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3′-untranslated region (3’UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. Conclusion ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.

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“…In addition, miR194 sponges could improve obesity-mediated cardiac dysfunction in vivo ( Nie et al, 2018 ). The expression of miR194 degraded coronary vascular tissues and endothelial cells of rats with atherosclerosis ( Li et al, 2021 ). Meanwhile, silencing miR-194-5p could alleviate doxorubicin-induced cardiotoxicity via PAK2 in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Panax notoginseng Saponins Alleviate Coronary Artery Disease Through Hypermethylation of the miR-194-MAPK Pathway

Duan

Liu

et al. 2022

Front. Pharmacol.

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Background:Panax notoginseng saponins (PNS) may have an inhibitory effect against coronary artery disease (CAD); however, the mechanism is unclear. Recent research has begun to evaluate the role of epigenetics in CAD. Our team found that hypomethylation of miR-194 could be an important mechanism of CAD.Purpose: The aim of this study was to investigate the effect of PNS against CAD and evaluate whether the mechanism is related to methylation of mi-R194.Methods: We conducted a randomized controlled trial with a double-blind placebo design on 84 patients with CAD. Treatment was continued for 4 weeks, and the clinical effect of PNS on CAD was observed. Methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured by pyrosequencing and qRT-PCR. We then conducted a pharmacological analysis of the active components of PNS. The effects of PNS on oxidized human umbilical vein endothelial cells and the methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured in vitro through methylation-specific PCR (MSPCR), qRT-PCR, Western blot analysis, and annexin V/propidium iodide apoptosis assay.Results: PNS improved symptoms of CAD. High-density lipoprotein and white blood cell count demonstrated significant changes after treatment in the PNS group. No significant difference was observed between miR-194 and mRNA MAPK, FAS, RAS, and FOS in the PNS group after treatment. However, some notable trends were observed in these genes. The targets of PNS were predicted by the pharmacological components. Some targets were found to be differentially expressed genes in CAD sequencing. Six genes, including MAPK1, RAS, and FASL, were common targets of PNS in CAD sequencing. Correlations were observed between genes in the interaction network and clinical parameters. In vitro experiments confirmed that PNS could change the methylation of miR-194, its promoter, and MAPK, FAS, RAS, and FOS. Intervention with PNS is likely to improve apoptosis.Conclusion: We reported the regulation of miR-194 promoter, miR-194, and MAPK methylation by PNS through cell experiments and a randomized controlled trial. PNS can be used for intervention in CAD by targeting the miR-194 promoter-miR-194-MAPK signaling pathway.Clinical Trial Registration: https://www.clinicaltrials.gov/, NCT03083119.

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Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis

Cited by 13 publications

References 36 publications

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

Exosomal miR-17-5p from adipose-derived mesenchymal stem cells inhibits abdominal aortic aneurysm by suppressing TXNIP-NLRP3 inflammasome

Panax notoginseng Saponins Alleviate Coronary Artery Disease Through Hypermethylation of the miR-194-MAPK Pathway

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