Identification of key genes and pathways involved in abdominal aortic aneurysm initiation and progression.

Abstract

The study aimed to assess the gene expression profile of biopsies obtained from the neck of human abdominal aortic aneurysm (AAA) and the main site of AAA dilatation and to investigate the molecular mechanism underlying the development of AAA. The microarray profile of GSE47472 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database. The GSE47472 was a microarray dataset of tissues from the aortic neck of AAA patients versus normal controls. The GSE57691 was a microarray dataset including the tissues from main site of AAA dilatation versus normal controls. Differentially expressed genes (DEGs) were chosen using the R package and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). The hub genes were identified in the protein-protein interaction (PPI) network. 342 upregulated DEGs and 949 downregulated DEGs were obtained from GSE47472. The upregulated DEGs were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved glycosaminoglycan degradation, vasopressin-regulated water reabsorption, and pyruvate metabolism. The hub genes in GSE47472 mainly include VAMP8, PTPRC, DYNLL1, RPL38, RPS4X, HNRNPA1, PRMT1, TGOLN2, PA2G4, and CUL2. From GSE57691, 248 upregulated DEGs and 1120 downregulated DEGs were selected. The upregulated DEGs of GSE57691 were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in metabolic process (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved the mitochondrial respiratory, respiratory chain complex, and respiratory chain. RPS15A, RPS5, RPL23, RPL27A, RPS24, RPL35A, RPS4X, RPL7, RPS25, and RPL21 were identified as the hub genes. At the early stage of AAA, the current study indicated the importance of glycosaminoglycan degradation and anaerobic metabolism. We also identified several hub genes closely related to AAA (VAMP8, PTPRC, DYNLL1, etc.). At the progression of the AAA, the dysfunctional mitochondria played a critical role in AAA formation and the RPS15A, RPS5, RPL23, etc., were identified as the hub genes.