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.

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.

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 angiotensin Ⅱ 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.

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.

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.

Stanford A型主动脉夹层（TAAD）是一种致命性心血管疾病，发病率和死亡率均较高，需紧急行手术治疗。由于其临床症状与急性冠脉综合征等疾病相似，常导致诊断延迟，寻找TAAD的潜在致病基因对早期诊断和改善预后至关重要。

本研究旨在通过整合生物信息学分析与实验验证，筛选TAAD枢纽（Hub）致病基因，并探讨其与免疫细胞浸润的关联。

从高通量基因表达（GEO）数据库下载GSE153434数据集，利用R语言软件Limma包进行差异表达分析，通过基因本体论（GO）、疾病本体论（DO）和KEGG富集分析揭示TAAD的潜在分子机制。筛选Hub基因，并在GSE52093数据集验证其表达一致性，绘制受试者工作特征（ROC）曲线评估诊断效能。18只C57BL/6小鼠，皮下埋置血管紧张素Ⅱ微量泵建立TAAD模型，收集主动脉组织，HE染色检测病变情况，进行实时荧光定量PCR（qPCR）验证，并利用CIBERSORT算法分析免疫细胞浸润差异及相关性。

共筛选出TAAD患者差异表达基因1 672个，其中上调基因1 064个，下调基因608个。功能富集分析显示其参与血管系统发育、炎症反应及细胞因子活性调控等生物过程，并涉及PI3K-Akt、钙离子信号通路等关键通路。12只小鼠建立TAAD模型，10只小鼠模型建立成功，其中4只小鼠因主动脉夹层导致死亡，剩余6只小鼠进行后续实验。HE染色显示对照（Con）组主动脉壁结构正常，弹力纤维完整。主动脉夹层（AD）组主动脉壁结构明显破坏，中膜层出现分离，弹性纤维断裂，真、假腔形成，腔内可见血栓。通过GSE52093数据集以及小鼠主动脉qPCR验证，分泌性磷蛋白1（SPP1）可能是TAAD病变的核心基因，其表达与巨噬细胞及T细胞等免疫细胞的浸润相关。

TAAD的发病机制与PI3K-Akt、钙离子信号通路及免疫微环境失调密切相关。SPP1可能作为TAAD的潜在生物标志物和治疗靶点，为早期诊断和免疫治疗提供了新的研究方向。未来需进一步开展多中心临床研究及分子机制探索验证其临床应用价值。