Low expression of integrin signaling pathway genes is associated with abdominal aortic aneurysm: a bioinformatic analysis by WGCNA

G.-M. Cao, X.-Z. Xuan, H.-L. Dong

Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. honglindong@sxmu.edu.cn

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• Cardiovascular Diseases
• Vascular Medicine

OBJECTIVE: An abdominal aortic aneurysm (AAA) is a potentially fatal disease associated with a high risk of rupture. AAA is pathologically distinguished by atherosclerotic thrombosis, immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Given that there are no effective target treatments, once ruptured, AAA leads to high mortality with few long-term survivors. The goal of this study is to identify novel key pathways and hub genes involved in AAA formation with the aim of providing promising therapeutic targets for AAA.

MATERIALS AND METHODS: The transcriptome sequencing matrix of GSE47472 and GSE57691 were obtained from the GEO database. These datasets were further merged for differential expression analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment analysis in R (v4.0.2). A co-expression network was constructed with Cytoscape (v3.8.0) to generate the top 30 hub genes. Hub Genes with high clinical traits and potential values were further verified using a receiver operating characteristic (ROC) curve and qPCR analysis.

RESULTS: A total of 745 differentially expressed genes were screened and 14 gene co-expression modules were established. Among these 14 modules, pink modules with a total of 118 genes showed the strongest correlation with AAA pathogenesis. Subsequently, 78 genes associated with a highly relevant clinical trait and the top 30 hub genes were intersected to generate 22 genes. Gene ontology functional enrichment analysis of the 22 genes revealed abnormal expression of genes relating to cell-matrix adhesion and integrin-mediated signaling pathway. LAMA5, ITGA8, ITGA1, and FERMT2 were associated with the integrin-mediated signaling pathway and cell-matrix adhesion while ACTN1 and CX3CL1 were simply associated with the latter. Low expressions of LAMA5, ACTN1, ITGA8, ITGA1, and FERMT2 were further verified through qPCR in a mouse model of AAA.

CONCLUSIONS: Low expression of partial genes in the integrin signaling pathway was implicated in the function loss of mediated cell-matrix adhesion, which may offer novel targets for therapeutic intervention against AAA.

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