AUTHOR=Wan Hong , Liu Danlingyi , Liu Bingqing , Sha Mengyao , Xia Wei , Liu Chang 

TITLE=Bioinformatics analysis of aging-related genes in thoracic aortic aneurysm and dissection

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1089312

DOI=10.3389/fcvm.2023.1089312

ISSN=2297-055X

ABSTRACT=Objective: Thoracic aortic aneurysm and dissection (TAAD) is a cardiovascular disease with a high mortality rate. Aging is an important risk factor for TAAD. We explored the relationship between aging and TAAD and investigated the mechanisms crucial for the diagnosis and treatment of TAAD. 
Results: We identified 70 DEGs associated with aging in TAAD. GO enrichment analysis revealed that the DEGs played a major role in regulating DNA metabolism and damaged DNA binding. KEGG enrichment analysis revealed enrichment in the longevity regulating pathway, cellular senescence, and HIF-1 signaling pathway. GSEA revealed that the DEGs were concentrated in the cell cycle and aging-related p53 signaling pathway. We screened five hubgenes: MYC, IL6, HIF1A, ESR1, and PTGS2.Single-cell sequencing of the aging rat aorta showed that HIF1A was up-regulated in M1 macrophages  and T Cell (TC) , and was down-regulated in fibroblast (Fib)  and B cell (BC) ; MYC was up-related in smooth muscle cell (SMC), Fib, endothelial cell (EC), and TC , and down-regulation in M2 macrophages; IL6 was up-regulated in SMC, Fib, and EC , and down-regulated in M1 macrophages ; PTGS2 was up-regulated in Fib and down-regulated in SMC, BC, M2 macrophages, EC, TC, and M1 macrophages ; ESR1 was down-regulated in Fib.  Among these five hubgenes，HIF1A and PTGS2 were validated in the aging dataset GSE102397 ; MYC、HIF1A and ESR1 were validated in the TAAD dataset GSE153434. The area under the diagnostic ROC curve showed that the combined AUC of these five hubgenens were > 0.7 in both testing set and training set were, suggesting that these five hubgenes had good specificity and sensitivity, with potential as an aging-related marker in TAAD.
Conclusion: The HIF-1 signaling pathway may play an important role in TAAD and aging. The combination of this five hubgens has potential as a biomarker of aging-related TAAD.