Role of ferroptosis-related genes in Stanford type a aortic dissection and identification of key genes: new insights from bioinformatic analysis

• Published in: Bioengineered Vol. 12; no. 2; pp. 9976 - 9990
• Main Authors: Zou, Hua-Xi, Qiu, Bai-Quan, Lai, Song-Qing, Huang, Huang, Zhou, Xue-Liang, Gong, Cheng-Wu, Wang, Li-Jun, Yuan, Ming-Ming, He, an-Di, Liu, Ji-Chun
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 20.12.2021
• Subjects: Algorithms; Animals; Aortic Dissection - genetics; Aortic Dissection - immunology; bioinformatics analysis; Cell Line; Computational Biology; Ferroptosis; Ferroptosis - genetics; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Humans; key genes; Muscle, Smooth, Vascular - injuries; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Protein Interaction Maps - genetics; Rats; Reproducibility of Results; Research Paper; Stanford type a aortic dissection; Ferroptosis; database; key genes; Stanford type a aortic dissection; bioinformatics analysis
• ISSN: 2165-5979; 2165-5987; 2165-5987
• DOI: 10.1080/21655979.2021.1988840

Stanford type A aortic dissection (TAAD) is one of the most dangerous vascular diseases worldwide, and the mechanisms of its development remain unclear. Further molecular pathology studies may contribute to a comprehensive understanding of TAAD and provide new insights into diagnostic markers and potential therapeutic targets. Recent studies have identified that ferroptosis, a form of cell death, may play a previously unrecognized role in influencing the development of TAAD. In this study, we explored the pathological role of ferroptosis in TAAD by performing bioinformatics analyses. Gene set enrichment analysis (GSEA) showed that the ferroptosis-related gene (FRG) set was significantly different between normal and TAAD aortic samples at an overall level (p < 0.001). Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses explored the potential functions and pathways of FRG in TAAD. We further identified six key genes (CA9, HMOX1, IL6, CDKN1A, HIF1A, MYC) from differentially expressed FRGs in TAAD by constructing a protein-protein interaction (PPI) network, all key genes were upregulated in TAAD. Four of the key genes (CA9, IL6, CDKN1A, and HIF1A) were demonstrated to be correlated with cigarette smoke extract-induced ferroptosis in aortic vascular smooth muscle cells. These results suggest that ferroptosis is one of the essential pathological processes in the development of TAAD, and some FRGs affect TAAD development by mediating cellular ferroptosis, which provides deepening insights into the molecular mechanisms and potential therapeutic targets of TAAD.