Ma Xianlu, Zhou Hongjie, Wang Ren
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Cardiac Vascular Surgery, Jining No.1 People's Hospital, Jining, China.
Front Cell Dev Biol. 2025 May 22;13:1554972. doi: 10.3389/fcell.2025.1554972. eCollection 2025.
Abdominal aortic aneurysm (AAA), characterized by the pathological dilation of the abdominal aorta, was associated with immune response and inflammation. However, the key genes involved in the occurrence and progression of AAA remains unclear.
We applied Weighted Gene Co-expression Network Analysis (WGCNA) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) to screen for significant genes from the Gene Expression Omnibus (GEO) dataset. The CIBERSORT algorithm was utilized to analyze the correlation between these genes and immune cell infiltration. Additionally, we validated the expression of FosB proto-oncogene, AP-1 transcription factor subunit (FOSB) in a murine model of AAA. FOSB was overexpressed and knocked out in vascular smooth muscle cells (VSMCs). Cell viability and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The levels of MMP2 and MMP9 in the cell supernatants were quantified by ELISA. The expression of contraction-related markers α-SMA and SM22α, and the synthetic marker OPN, was analyzed by qRT-PCR and Western blot.
A total of 44 differentially expressed genes were identified, revealing distinct expression patterns between AAA and normal samples. WGCNA identified two key gene modules that were strongly correlated with immune and inflammatory responses, with the hub genes from these modules enriched in immune-related pathways. FOSB was positively correlated with monocytes, plasma cells, eosinophils, and T follicular helper cells. It was further validated in an AngII-induced AAA mouse model. Overexpression of FOSB significantly increased the expression levels of MMP2 and MMP9 in VSMCs. Additionally, FOSB overexpression inhibited the expression of contractile phenotype markers α-SMA and SM22α, while promoting the expression of synthetic phenotype marker OPN.
Exosome-related gene FOSB was involved in the progression of abdominal aortic aneurysm. FOSB represents a promising potential therapeutic target for mitigating the progression of Abdominal Aortic Aneurysm.
腹主动脉瘤（AAA）以腹主动脉的病理性扩张为特征，与免疫反应和炎症相关。然而，参与AAA发生和发展的关键基因仍不清楚。
我们应用加权基因共表达网络分析（WGCNA）和支持向量机递归特征消除（SVM-RFE）从基因表达综合数据库（GEO）数据集中筛选重要基因。利用CIBERSORT算法分析这些基因与免疫细胞浸润之间的相关性。此外，我们在AAA小鼠模型中验证了原癌基因FosB、AP-1转录因子亚基（FOSB）的表达。在血管平滑肌细胞（VSMC）中过表达和敲除FOSB。分别使用CCK-8测定法和流式细胞术评估细胞活力和凋亡。通过ELISA定量细胞上清液中MMP2和MMP9的水平。通过qRT-PCR和蛋白质免疫印迹分析收缩相关标志物α-SMA和SM22α以及合成标志物OPN的表达。
共鉴定出44个差异表达基因，揭示了AAA与正常样本之间不同的表达模式。WGCNA确定了两个与免疫和炎症反应密切相关的关键基因模块，这些模块中的枢纽基因富集于免疫相关途径。FOSB与单核细胞、浆细胞、嗜酸性粒细胞和滤泡辅助性T细胞呈正相关。在血管紧张素II诱导的AAA小鼠模型中进一步验证了这一结果。FOSB的过表达显著增加了VSMC中MMP2和MMP9的表达水平。此外，FOSB的过表达抑制了收缩表型标志物α-SMA和SM22α的表达，同时促进了合成表型标志物OPN的表达。
外泌体相关基因FOSB参与了腹主动脉瘤的进展。FOSB是减轻腹主动脉瘤进展的一个有前景的潜在治疗靶点。
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