Stanford A型主动脉夹层病变关键基因筛选与免疫浸润研究OA

Background Stanford type A aortic dissection(TAAD)is a life-threatening cardiovascular condition with high morbidity and mortality,requiring emergency surgical intervention.Due to the similarity of its clinical manifestations with other diseases such as acute coronary syndrome,diagnosis is often delayed.Identifying potential pathogenic genes of TAAD is crucial for early diagnosis and improving prognosis.Objective This study aims to identify hub pathogenic genes in TAAD through integrated bioinformatics analysis and experimental validation,and to explore their association with immune cell infiltration.Methods The GSE153434 dataset was downloaded from the gene expression omnibus(GEO)database.Differential expression analysis was performed using the Limma package in R.gene ontology(GO),disease ontology(DO),and KEGG enrichment analyses were conducted to elucidate the underlying molecular mechanisms of TAAD.Hub genes were screened and validated for expression consistency using the GSE52093 dataset.Receiver operating characteristic(ROC)curves were plotted to evaluate diagnostic performance.A TAAD model was established in 18 C57BL/6 mice via subcutaneous implantation of an angiotensinⅡ micro-osmotic pump.Aortic tissues were collected,and pathological changes were examined by hematoxylin and eosin(HE)staining.Quantitative real-time PCR(qPCR)was performed for validation.Immune cell infiltration differences and correlations were analyzed using the CIBERSORT algorithm.Results A total of 1 672 differentially expressed genes were identified in TAAD patients,including 1 064 upregulated and 608 downregulated genes.Functional enrichment analysis revealed their involvement in biological processes such as vascular system development,inflammatory response,and cytokine activity regulation,as well as key pathways including the PI3K-Akt and calcium signaling pathways.The TAAD model was successfully established in 10 out of 12 mice,with 4 mice dying due to aortic dissection.The remaining 6 mice were used for subsequent experiments.HE staining showed normal aortic wall structure and intact elastic fibers in the control(Con)group,whereas the aortic dissection(AD)group exhibited significant structural disruption,medial layer separation,elastic fiber fragmentation,and formation of true and false lumens with intraluminal thrombus.Validation via the GSE52093 dataset and mouse aortic qPCR indicated that secreted phosphoprotein 1(SPP1)may serve as a core gene in TAAD pathogenesis,with its expression correlated with infiltration of immune cells such as macrophages and T cells.Conclusion The pathogenesis of TAAD is closely associated with dysregulation of the PI3K-Akt and calcium signaling pathways,as well as immune microenvironment imbalance.SPP1 may serve as a potential biomarker and therapeutic target for TAAD,providing new research directions for early diagnosis and immunotherapy.Further multicenter clinical studies and molecular mechanism investigations are warranted to validate its clinical applicability.