Underlying Genes Involved in Atherosclerotic Macrophages: Insights from Microarray Data Mining

Abstract

Background: In an atherosclerotic artery wall, monocyte-derived macrophages are the principal mediators that respond to pathogens and inflammation. The present study aimed to investigate potential genetic changes in gene expression between normal tissue-resident macrophages and atherosclerotic macrophages in the human body. Material/Methods: The expression profile data of GSE7074 acquired from the Gene Expression Omnibus (GEO) database, which includes the transcriptome of 4 types of macrophages, was downloaded. Differentially expressed genes (DEGs) were identified using R software, then we performed functional enrichment, protein-protein interaction (PPI) network construction, key node and module analysis, and prediction of microRNAs (miRNAs)/transcription factors (TFs) targeting genes. Results: After data processing, 236 DEGs were identified, including 21 upregulated genes and 215 downregulated genes. The DEG set was enriched in 22 significant Gene Ontology (GO) terms and 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the PPI network constructed with these DEGs comprised 6 key nodes with degrees ³8. Key nodes in the PPI network and simultaneously involved in the prime modules, including rhodopsin (RHO), coagulation factor V (F5), and bestrophin-1 (BEST1), are promising for the prediction of atherosclerotic plaque formation. Furthermore, in the miRNA/TF-target network, hsa-miR-3177-5p might be involved in the pathogenesis of atherosclerosis via regulating BEST1, and the transcription factor early growth response-1 (EGR1) was found to be a potential promoter in atherogenesis. Conclusions: The identified key hub genes, predicted miRNAs/TFs, and underlying molecular mechanisms may be involved in atherogenesis, thus potentially contributing to the treatment and diagnosis of patients with atherosclerotic disease.

Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification

“…This gene is also known as PSMD6-AS2, a gene that could disrupt expression of a proteasome subunit. This gene was identified as differentially expressed in a study of atherosclerotic macrophages [ 40 ]. Another proteasomal subunit, PSMC3 mutation is associated with subcutaneous calcifications [ 41 ], indicating that this lincRNA RP11-245 J9.5 might be involved in atherosclerosis by regulating several proteasome subunits.…”

Identification of Molecular Subtypes and Key Genes of Atherosclerosis Through Gene Expression Profiles

“…Huang et al discovered three differentially expressed genes ( KDELR3 , CD55 , and DYNC2H1 ) can serve as diagnostic and therapeutic targets in AS macrophages through microarray analysis ( Huang et al, 2019 ). Wang et al (2019) constructed a miRNA-TF-gene network through microarray data analysis in the AS macrophages. However, these studies only concentrated on the characterization of potential biomarkers, and the samples size of the dataset is small, which leads to low accuracy.…”

<p>LncRNA PVT1 Suppresses the Progression of Renal Fibrosis via Inactivation of TGF-β Signaling Pathway</p>

“…MiRNAs are highly conserved ncRNAs that exert versatile biological functions. [36][37][38] Wu et al indicated that PVT1 silencing could prevent the development of uveal melanoma through impairing miR-17-3p-dependent MDM2 upregulation. 39 Furthermore, PVT1 could modulate the proliferation and apoptosis of lens epithelial cells in diabetic cataract through regulation miR-214-3p/MMP2 axis.…”