Abstract
BackgroundAtherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). It is one of the most important causes of death worldwide. According to the inflammatory response theory, macrophages play a critical role in AS. However, the potential targets associated with macrophages in the development of AS are still obscure. This study aimed to use bioinformatics tools for screening and identifying molecular targets in AS macrophages.MethodsTwo expression profiling datasets (GSE7074 and GSE9874) were obtained from the Gene Expression Omnibus dataset, and differentially expressed genes (DEGs) between non-AS macrophages and AS macrophages were identified. Functional annotation of the DEGs was performed by analyzing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. STRING and Cytoscape were employed for constructing a protein–protein interaction network and analyzing hub genes.ResultsA total of 98 DEGs were distinguished between non-AS macrophages and AS macrophages. The functional variations in DEGs were mainly enriched in response to hypoxia, respiratory gaseous exchange, protein binding, and intracellular, ciliary tip, early endosome membrane, and Lys63-specific deubiquitinase activities. Three genes were identified as hub genes, including KDELR3, CD55, and DYNC2H1.ConclusionHub genes and DEGs identified by using microarray techniques can be used as diagnostic and therapeutic biomarkers for AS.
Highlights
Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS)
Differentially expressed gene (DEG) identified between non-AS- and AS-macrophages samples After analyzing the GSE7074 and GSE9874 datasets by using GEO2R, the differences between non-AS- and AS-macrophage samples were plotted in the form of volcano plots (Figs. 1 a,b)
Functional annotation of DEGs by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis The results of GO analysis demonstrated that the variations in biological process (BP), cellular component (CC), and molecular function (MF) of the DEGs were mainly enriched in negative regulation of Target of rapamycin (TOR) signaling, response to hypoxia, respiratory gaseous exchange, thiol-dependentubiquitin-specific protease activity, protein binding, Lys63-specific deubiquitinase activity, and intracellular, ciliary tip, and early endosome membrane activities (Table 1)
Summary
Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). According to the World Health Organization, 17 million people died of ASCVD worldwide in 2008, accounting for 30% of the total disease mortality, 80% of which occurred in low- and AS is an arterial disease associated with dyslipidemia and changes in the components of blood vessel walls. It mainly affects large and medium-sized arteries—especially those in the heart, brain, kidneys, and other organs—and can cause ischemic changes [4].
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