Comparative bioinformatics analysis of transcriptomes between β-aminopropionitrile-induced aortic dissection murine model and human aortic dissection

Ke Hu; Yi Guo; Yuxuan Li; Shunchang Zhou; Yiqing Li; Weici Wang

doi:10.21037/jtd-23-981

Comparative bioinformatics analysis of transcriptomes between β-aminopropionitrile-induced aortic dissection murine model and human aortic dissection

J Thorac Dis. 2023 Nov 30;15(11):6058-6071. doi: 10.21037/jtd-23-981. Epub 2023 Nov 27.

Authors

Ke Hu^#¹, Yi Guo^#¹, Yuxuan Li^#¹, Shunchang Zhou², Yiqing Li¹, Weici Wang¹

Affiliations

¹ Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Center of Experimental Animals, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Background: Aortic dissection (AD) poses a great threat to the life of patients; however, there is currently no documentation of a clear pathogenic mechanism of this disease. In recent years, β-aminopropionitrile (BAPN)-induced AD in rodents has been widely used in basic research, which provides a good platform for exploring the pathogenesis of AD and drug modification. This study aimed to identify molecular markers and pathways for the diagnosis and treatment of AD by comparing a murine AD model and human AD transcriptome through a bioinformatics analysis.

Methods: We constructed a BAPN-induced mice model and performed high-throughput sequencing analysis. The GSE147026 dataset of patients was obtained from the Gene Expression Omnibus database. We performed a subsequent bioinformatics analysis of human AD and the murine AD model using R software. The DESeq software package was used to analyze the differentially expressed genes (DEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to analyze the enrichment pathways. Protein-protein interaction network construction and hub gene selection were based on STRING software analysis. Stepwise identification of potential drugs was performed online, while hub genes were validated immunohistochemically.

Results: We compared the murine AD model and human AD transcriptome and found that both differentially expressed 463 genes. The cytokine-cytokine receptor interaction, tuberculosis, and phagosome pathways were significantly enriched. CDC20, CCNB2, and CCNB1 may be associated with AD development. Protein-drug interactions were also identified.

Conclusions: This study is the first to reveal transcriptional changes in a murine BAPN-induced AD model versus human AD transcriptome. Furthermore, we identified the important hub genes, related pathways, and potential drugs by analyzing the overlapping DEGs between human AD and the murine AD model. Our results provide a basis for the further identification of potential molecular markers for diagnosing and treating AD.

Keywords: Aortic dissection (AD); animal model; bioinformatics analysis; β-aminopropionitrile (BAPN).