Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques

作者：Jinrui Ren, Yanze Lv, Lianglin Wu, Siliang Chen, Chuxiang Lei, Dan Yang, Fangda Li, Changzheng Liu, Yuehong Zheng · 发表于：Frontiers in Cardiovascular Medicine · 年份：2022 · DOI：10.3389/fcvm.2022.875434 · 被引用次数：34 · 研究领域：Aortic aneurysm repair treatments、Ferroptosis and cancer prognosis、interferon and immune responses

Objectives Abdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown. Methods GSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein–protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE –/– and CD57B/6J mice by immunofluorescence assay. Results In AAA and normal samples, 40 FDEGs were identified, and the expression of supp...