FOS gene associated immune infiltration signature in perivascular adipose tissues of abdominal aortic aneurysm
FOS gene associated immune infiltration signature in perivascular adipose tissues of abdominal aortic aneurysm
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DOI：
10.1016/j.gene.2022.146576
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发表时间：
2022-05-16
期刊：
影响因子：
3.5
通讯作者：
Yuan, Zhidong
中科院分区：
文献类型：
--
作者：
Ding, Suping;Gan, Tao;Yuan, Zhidong
腹主动脉瘤（AAA）是局部主动脉壁的病理性扩张。 AAA 周围血管周围脂肪组织 (PAT) 的炎症浸润与 AAA 相关，并且已被证明有助于血管病理学。然而，PAT 炎症导致 AAA 血管病理的机制仍有待阐明。本研究旨在探讨 AAA 的 PAT 中免疫细胞浸润与关键基因表达谱之间的关联。为此，从GEO下载了人类扩张血管周围脂肪组织（dPAT）、非扩张血管周围脂肪组织（ndPAT）、腹部皮下脂肪（SAF）和网膜内脏脂肪（OVF）样本的基因表达数据集，以及外周动脉疾病患者腹部血管周围脂肪组织的另一个微阵列数据集 用于本研究分析的数据库。 CIBERSORT算法、加权基因共表达网络分析（WGCNA）和LASSO算法用于免疫浸润、免疫相关基因的识别和诊断特征的开发。我们的数据发现，dPAT 样品中活化的肥大细胞和滤泡辅助 T (Tfh) 细胞的比例明显高于 ndPAT、OVT 和 SAF 样品。此外，AP-1家族成员（FOS、FOSB、ATF3、JUN和JUNB）被发现组成WGCNA中紫色模块的中心基因。其中，FOS基因作为区分AAA中的dPAT与ndPAT、OVT和SAF的更有效标记。同时，AP-1家族成员的表达谱均与AAA dPAT中活化的肥大细胞、浆细胞和Tfh细胞浸润呈显着正相关。因此，在 AAA 周围的 PAT 中，炎症浸润的特征可能表现为 FOS 主导的细胞网络，由活化的肥大细胞、浆细胞和 Tfh 细胞组成。鉴于 AAA 的复杂病因，我们的结果可能为局部 dPAT 影响 AAA 的病理生理机制提供新的线索。
Abdominal aortic aneurysms (AAA) are pathological dilations in local aortic wall. The inflammatory infiltrates of the perivascular adipose tissue (PAT) surrounding AAAs were associated with AAAs and have been shown to contribute vascular pathology. However, the mechanism by which PAT inflammation contributes to vascular pathology in AAA remains to be clarified. This study aimed to explore the association between immune cell infiltration and key gene expression profile in PAT of AAA. For that, a gene expression dataset of human dilated perivascular adipose tissue (dPAT), non-dilated perivascular adipose tissue (ndPAT), subcutaneous abdominal fat (SAF) and omental-visceral fat (OVF) samples, as well as another microarray dataset of the abdominal perivascular adipose tissue in peripheral artery disease patients were downloaded from GEO database for analysis in this study. The CIBERSORT algorithm, weighted gene co-expression network analysis (WGCNA) and LASSO algorithm were used for the identification of immune infiltration, immune-related genes and the development of diagnostic signature. Our data discovered a significant higher proportion of activated mast cells and follicular helper T (Tfh) cells in dPAT than ndPAT, OVT and SAF samples. Moreover, AP-1 family members (FOS, FOSB, ATF3, JUN and JUNB) were found to compose the hub genes of purple module in WGCNA. Among them, FOS gene acts as a higher efficient marker to discriminate dPAT from ndPAT, OVT and SAF in AAA. Meanwhile, the expression profiles of the AP-1 family members are all significantly positive correlated with activated mast cell, plasma cell and Tfh cell infiltration in dPAT of AAA. Therefore, in the PAT surrounding AAA, the signature of inflammatory infiltration might be represented by a FOS-dominated cell network consist of activated mast cell, plasma cell and Tfh cell. Given the complicated etiology of AAA, our results are likely to shed new light on the pathophysiologic mechanism of AAA influenced by the local dPAT.