Utilizing Integrated Bioinformatics Analysis to Explore Potential Alterations in Mitochondrial Function Within Immune...

Thoracic aortic aneurysm (TAA) is a life-threatening peripheral vascular disease with a complex pathogenesis. Altered mitochondrial function in vascular smooth muscle cells has been implicated in TAA development. However, the link between mitochondrial functional status and immune cell behavior in TAA patients remains largely unexplored. In this study, we analyzed several bulk RNA-seq and snRNA-seq datasets of TAA from the NCBI-GEO and Genome Sequence Archive database, identifying differentially expressed mitochondrial-related genes (DE-MRGs). To assess mitochondrial function, we calculated a mitoscore to represent the overall expression level of MRGs. Our analysis revealed mitochondrial-mediated apoptosis occurring in M1 macrophages, while CD4 + T cells demonstrated the activation of quality control mechanisms, such as mitochondrial fission. Through LASSO regression and SVM-RFE, we identified key MRGs, including MUCB, ARRB2, FRG, and ALPL, which we further validated using TAA mouse models. Additionally, we found that DE-MRGs were closely linked to methionine metabolism. In conclusion, this study highlights mitochondrial dysfunction in immune cells associated with TAA, shedding light on potential mitochondrial roles in TAA pathogenesis.