CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-cateninT120/TCF21 pathway

Gao, Jiahui; He, Lin-Hao; Yu, Xiaohua; Zhao, Zhen-Wang; Wang, Gang; Zou, Jin; Wen, Feng-Jiao; Zhou, Li; Wan, Xiang-Jun; Zhang, Da Wei; Tang, Chao-Ke

doi:10.1194/jlr.ra119000100

Cited by 44 publications

(41 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we applied the bioinformatics method to construct the LINC00968-related ceRNA regulatory network, which provides new ideas for exploring the biological functions of LINC00968. From the constructed LIN00968 related ceRNA network, we found several mRNAs which have been previously reported to play a role in atherosclerosis, such as CXCL12 29 , TAZ 30 , PDLIM5 31 , GNB3 32 , LMNA 33 , TRPM6 34 . Similarly, we used bioinformatics to predict the top five key mRNAs in the LINC00968-related ceRNA network, including GNG13, GNB3, CXCL12, ADCY3 and LMNA, among which CXCL12 and LMNA were significantly dysregulated in CAD according to verification results.…”

Section: Discussionmentioning

confidence: 99%

lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease

Wang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Epicardial adipose tissue (EAT) contributes to the pathophysiological process of coronary artery disease (CAD). The expression profiles of long non-coding RNAs (lncRNA) in EAT of patients with CAD have not been well characterized. We conducted high-throughput RNA sequencing to analyze the expression profiles of lncRNA in EAT of patients with CAD compared to patients without CAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. We confirmed a dysregulated intergenic lncRNA (lincRNA) (LINC00968) by real-time quantitative PCR (RT-qPCR). Subsequently, we constructed a ceRNA network associated with LINC00968, which included 49 mRNAs. Compared with the control group, lncRNAs and genes of EAT in CAD were characterized as metabolic active and pro-inflammatory profiles. The sequencing analysis detected 2539 known and 1719 novel lncRNAs. Then, we depicted both lncRNA and gene signatures of EAT in CAD, featuring dysregulation of genes involved in metabolism, nuclear receptor transcriptional activity, antigen presentation, chemokine signaling, and inflammation. Finally, we identified a ceRNA network as candidate modulator in EAT and its potential role in CAD. We showed the expression profiles of specific EAT lncRNA and mRNA in CAD, and a selected non-coding associated ceRNA regulatory network, which taken together, may contribute to a better understanding of CAD mechanism and provide potential therapeutic targets.Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024782.

show abstract

Section: Discussionmentioning

confidence: 99%

lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease

Wang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Its role in the context of atherosclerosis, however, has not yet been fully clarified. While the two main risk alleles have been associated with higher CXCL12 plasma levels [ 64 ] and two recent studies in mice suggest CXCL12 promotes atherosclerosis [ 65 , 66 ], the CXCL12 receptor CXCR4 has been shown to be atheroprotective in studies, when its function was being disturbed [ 67 , 68 ]. In mice with myocardial infarction, however, pharmacologically inhibiting CXCR4 has been shown to be beneficial due to improved infarct repair by augmented regulatory T cell function [ 69 ].…”

Section: Genetic Variants In Cad Linked To Inflammationmentioning

confidence: 99%

Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease

Mauersberger

Schunkert

Sager

2021

Cells

View full text Add to dashboard Cite

Although the importance of inflammation in atherosclerosis is now well established, the exact molecular processes linking inflammation to the development and course of the disease are not sufficiently understood. In this context, modern genetics—as applied by genome-wide association studies (GWAS)—can serve as a comprehensive and unbiased tool for the screening of potentially involved pathways. Indeed, a considerable proportion of loci discovered by GWAS is assumed to affect inflammatory processes. Despite many well-replicated association findings, however, translating genomic hits to specific molecular mechanisms remains challenging. This review provides an overview of the currently most relevant inflammation-related GWAS findings in coronary artery disease and explores their potential clinical perspectives.

show abstract

“…Except for the above pathway, Sylvia et al found that TCF21 could bind to the VSMC marker ACTA2 locus and blocks its expression, indicating a directly inhibiting effect of TCF21 on some VSMC genes (Nurnberg et al, 2015). Also, the downregulated TCF21 expression induced by CXCL12 could decrease the promoter activity of ABCA1 and ABCA1 expression, thus inhibiting ABCA1-dependent cholesterol efflux from macrophages and promoting atherosclerosis (Gao et al, 2019).…”

Section: The Downstream Pathways Of Tcf21 In Vsmc Phenotypic Modulationmentioning

confidence: 99%

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Shen

Wang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Transcription factor 21 (TCF21) is specific for mesoderm and is expressed in the embryos' mesenchymal derived tissues, such as the epicardium. It plays a vital role in regulating cell differentiation and cell fate specificity through epithelial-mesenchymal transformation during cardiac development. For instance, TCF21 could promote cardiac fibroblast development and inhibit vascular smooth muscle cells (VSMCs) differentiation of epicardial cells. Recent large-scale genome-wide association studies have identified a mass of loci associated with coronary heart disease (CHD). There is mounting evidence that TCF21 polymorphism might confer genetic susceptibility to CHD. However, the molecular mechanisms of TCF21 in heart development and CHD remain fundamentally problematic. In this review, we are committed to providing a detailed introduction of the biological roles of TCF21 in epicardial fate determination and the development of CHD.

show abstract

CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-cateninT120/TCF21 pathway

Abstract: Tang. CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3/-cateninT120/ TCF21 pathway.

Cited by 44 publications

References 54 publications

lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease

lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease

Inflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Contact Info

Product

Resources

About