Inhibition of long noncoding RNA HIF1A-AS2 confers protection against atherosclerosis via ATF2 downregulation

Li, Pengcheng; Xing, Junhui; Zhang, Jielei; Jiang, Jianwu; Liu, Xuemeng; Zhao, Di; Zhang, Yanzhou

doi:10.1016/j.jare.2020.07.015

Cited by 29 publications

(29 citation statements)

References 35 publications

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“…ATF2 has been reported to be involved in the regulation of inflammation in atherosclerosis. For example, the downregulation of long non-coding RNA HIF1A antisense RNA 2 has been shown to inhibit atherosclerotic inflammation by suppressing ATF2 [ 33 ]. Another study showed that ATF2 regulates anti-inflammatory activity [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Protein disulfide-isomerase A3 knockdown attenuates oxidized low-density lipoprotein-induced oxidative stress, inflammation and endothelial dysfunction in human umbilical vein endothelial cells by downregulating activating transcription factor 2

et al. 2022

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Atherosclerosis is a chronic inflammatory disease implicated in oxidative stress and endothelial dysfunction. Protein disulfide-isomerase A3 (PDIA3) has been reported to regulate oxidative stress and suppress inflammation. This study aimed to explore the function of PDIA3 in atherosclerosis and the underlying mechanisms. PDIA3 expression in oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was detected using RT-qPCR and Western blotting. Following PDIA3 knockdown through transfection with small interfering RNA targeting PDIA3, cell viability, oxidative stress and inflammation in ox-LDL-induced HUVECs was examined using a Cell Counting Kit-8, corresponding kits and ELISA, respectively. The levels of CD31, α-smooth muscle, iNOS, p-eNOS, eNOS and NO were assessed using RT-qPCR, Western blotting and an NO kit to reflect endothelial dysfunction in ox-LDL-induced HUVECs. The relationship between PDIA3 and the activating transcription factor 2 (ATF2) was confirmed using co-immunoprecipitation. In addition, ATF2 expression was examined following PDIA3 silencing. The results indicated that PDIA3 was highly expressed in ox-LDL-induced HUVECs. PDIA3 silencing increased cell viability, and reduced oxidative stress and inflammation, as evidenced by the decreased levels of reactive oxygen species, malondialdehyde, TNF-α, IL-1β and IL-6, and increased superoxide dismutase and glutathione peroxidase activity. In addition, PDIA3 deletion improved endothelial dysfunction. PDIA3 interacted with ATF2, and PDIA3 deletion downregulated ATF2 expression. Furthermore, ATF2 overexpression reversed the effects of PDIA3 knockdown on ox-LDL-induced damage of HUVECs. Collectively, PDIA3 knockdown was found to attenuate ox-LDL-induced oxidative stress, inflammation and endothelial dysfunction in HUVECs by downregulating ATF2 expression, showing promise for the future treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Protein disulfide-isomerase A3 knockdown attenuates oxidized low-density lipoprotein-induced oxidative stress, inflammation and endothelial dysfunction in human umbilical vein endothelial cells by downregulating activating transcription factor 2

et al. 2022

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“…Silencing of USF1 expression increases the expression of VEGF ( 55 ). In addition, Li et al proved that inhibiting the expression of USF1 significantly reduces the expression of inflammatory factors such as IL-1β, TNF-α, and IL-6, thereby alleviating atherosclerotic inflammatory responses ( 56 ). Therefore, USF1 may be involved in atherosclerosis by regulating the expression of IL-1β, VEGF, TNF-α, and IL-6.…”

Section: Discussionmentioning

confidence: 99%

Effects of USF1 SNPs and SNP–Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population

Zheng

Chen²,

Pan³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundUpstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China.MethodsSix USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD.ResultsThe genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C–rs2774276G–rs2516839A and rs3737787C–rs2774276G–rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C–rs2774276G–rs2516839A and rs3737787T–rs2774276C–rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05–0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (pI < 0.001). The expression levels of the USF1 mRNA, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1β, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1β, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01).ConclusionSex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1β, TNF-α, and IL-6.

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“…In this study, we found that ATF2 is highly correlated with neutrophils and endothelial cells, suggesting that leukocyte-endothelial adhesion also appears in the IDD immune response, reflecting a characteristic of the changes in the IDD immune microenvironment. ATF2 mainly participates in the inflammatory response through the JNK and p38 MAP kinase pathways [ 47 ]. The low expression of ATF2 can lead to the excessive activation of the immune system and the massive invasion of T cells [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

SNHG5/miR-299-5p/ATF2 Axis as a Biomarker in Immune Microenvironment of Intervertebral Disc Degeneration

Shi

Guo

Fang

et al. 2022

Mediators of Inflammation

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Background and Objective. Intervertebral disc degeneration (IDD) is closely related to back pain. Finding biomarkers of IDD is very helpful for maintaining the function of the intervertebral disc and reducing the occurrence of back pain. This study is to explore the biomarkers in IDD and to explore the role of immune cell infiltration in IDD. Methods. The data sets of GSE56081 and GSE63492 in the Gene Expression Omnibus (GEO) database were used for screening and analysis, and the key gene markers were verified by GSE34095 and GSE126883. Finally, the infiltration of immune cells in the data were analyzed by MCPcounter analysis package. Results. In this study, a ceRNA containing 15 lncRNAs, 9 miRNAs, and 103 mRNAs was constructed. After multimodel screening and verification, key gene marker was found, namely, ATF2. The lncRNA/miRNA/mRNA axis closely related to ATF2 have also been found, namely, SNHG5/miR-299-5p/ATF2. In the analysis of immune infiltration, ATF2 was negatively correlated with T cells but positively correlated with neutrophils and endothelial cells. Conclusion. The SNHG5/miR-299-5p/ATF2 can be used as biomarker of IDD, and infiltration of immune cells plays an important role in the pathological development of IDD. In addition, as a marker of IDD, the involvement of the above-mentioned axis in the pathological development of IDD remains to be further explored.

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Inhibition of long noncoding RNA HIF1A-AS2 confers protection against atherosclerosis via ATF2 downregulation

Cited by 29 publications

References 35 publications

Protein disulfide-isomerase A3 knockdown attenuates oxidized low-density lipoprotein-induced oxidative stress, inflammation and endothelial dysfunction in human umbilical vein endothelial cells by downregulating activating transcription factor 2

Protein disulfide-isomerase A3 knockdown attenuates oxidized low-density lipoprotein-induced oxidative stress, inflammation and endothelial dysfunction in human umbilical vein endothelial cells by downregulating activating transcription factor 2

Effects of USF1 SNPs and SNP–Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population

SNHG5/miR-299-5p/ATF2 Axis as a Biomarker in Immune Microenvironment of Intervertebral Disc Degeneration

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