Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No 1. Shuaifuyuan, Dongcheng District, Beijing, China.
Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Gene. 2020 Dec 15;762:145056. doi: 10.1016/j.gene.2020.145056. Epub 2020 Aug 15.
Abdominal aortic aneurysm (AAA) is a disease characterized by weakening arterial wall and permanent expansion with high mortality once rupture, which was involved with immune system activation. However, owing to technical difficulties, previous research has limited the impact of one or limited immune cells on AAA.
We analyzed the composition of immune cells using the CIBERSORT algorithm through transcriptome sequencing data from patients with stable (eAAA) and ruptured aneurysms (rAAA). The whole transcriptome sequencing data, including 17 patients with ruptured AAA and 31 patients with stable AAA were downloaded from Gene Expression Omnibus (GEO, GSE98278). After normalizing and data processing, five rAAA and seventeen eAAA patients entered the follow-up analysis. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify several pathways that were significantly enriched in rAAA compared to eAAA tissues.
We demonstrated that the compositions of infiltrative immune cell in eAAA and rAAA were different. Naïve B cells, both resting and activated CD4+ memory T cells were found significantly higher in ruptured AAA, while memory B cells and activated mast cells were much less in ruptured AAA than that in stable AAA. Besides, PTX3 was significantly highly expressed in rAAA, which might be associated with the complement system and polarization of macrophages. Finally, differentially expressed genes and the related immune cells were mapped in a network to reveal the relationship between gene expression and infiltrative immune cells.
We identified the infiltrated immune cell profile of eAAA and rAAA patients, which might be the potential target of AAA treatment.
腹主动脉瘤（AAA）是一种以动脉壁变弱和永久性扩张为特征的疾病，一旦破裂死亡率很高，这与免疫系统的激活有关。然而，由于技术上的困难，以前的研究仅限于一种或有限的免疫细胞对 AAA 的影响。
我们通过对稳定（eAAA）和破裂性动脉瘤（rAAA）患者的转录组测序数据，使用 CIBERSORT 算法分析免疫细胞的组成。全转录组测序数据，包括 17 例破裂性 AAA 和 31 例稳定 AAA 患者，从基因表达综合数据库（GEO，GSE98278）下载。在进行归一化和数据处理后，5 例 rAAA 和 17 例 eAAA 患者进入随访分析。我们进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以确定与 eAAA 组织相比，rAAA 组织中明显富集的几个途径。
我们表明，eAAA 和 rAAA 中浸润性免疫细胞的组成不同。在破裂性 AAA 中，幼稚 B 细胞和静息及激活的 CD4+记忆 T 细胞显著升高，而记忆 B 细胞和激活的肥大细胞在破裂性 AAA 中明显低于稳定 AAA。此外，rAAA 中 PTX3 的表达显著升高，这可能与补体系统和巨噬细胞的极化有关。最后，差异表达基因及其相关免疫细胞被映射到一个网络中，以揭示基因表达与浸润性免疫细胞之间的关系。
我们确定了 eAAA 和 rAAA 患者浸润性免疫细胞的特征，这可能是 AAA 治疗的潜在靶点。
