Identification of monocyte-associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics-data.
Identification of monocyte-associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics-data.
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DOI：
10.1002/pul2.12319
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发表时间：
2023-10
影响因子：
2.6
通讯作者：
Tang, Hao
中科院分区：
文献类型：
--
作者：
Zhong, Caiming;Si, Yachen;Yang, Huanhuan;Zhou, Chao;Chen, Yang;Wang, Chen;Liu, Yalong;Chen, Cheng;Shi, Hui;Lai, Xueli;Tang, Hao
关键词：
肺动脉高压（PAH）是一种可导致心力衰竭的慢性、难治性疾病。免疫微环境在PAH中起重要作用。本研究的目的是评估免疫细胞浸润在PAH发病机制中的作用。基于微阵列数据的差异表达基因在几个免疫相关通路中富集。为了评估免疫细胞浸润，基于GEO数据库中的微阵列数据集，我们使用ssGSEA和CIBERSORT算法。此外，单细胞RNA测序（scRNA-seq）数据被用于进一步明确特定作用和细胞间通讯。然后使用受试者操作特征曲线和最小绝对收缩和选择算子来发现和测试PAH的潜在诊断生物标志物。基于微阵列数据集的免疫细胞浸润分析和scRNA-seq数据中的细胞比例均显示PAH中单核细胞浸润显著下调。然后，细胞间通讯显示，包括单核细胞在内的大多数免疫细胞的相互作用权重在对照组和PAH组之间发生了变化，ITGAL‐ ITGB 2和ICAM信号通路在此过程中发挥了关键作用。ITGAM和ICAM 2对PAH有较好的诊断价值。提示单核细胞的变化是PAH的重要免疫学特征之一。单核细胞相关ICAM-1和ITGAL-ITGB 2信号通路可能参与PAH的发病机制。
Pulmonary arterial hypertension (PAH) is one kind of chronic and uncurable diseases that can cause heart failure. Immune microenvironment plays a significant role in PAH. The aim of this study was to assess the role of immune cell infiltration in the pathogenesis of PAH. Differentially expressed genes based on microarray data were enriched in several immune‐related pathways. To evaluate the immune cell infiltration, based on the microarray data sets in the GEO database, we used both ssGSEA and the CIBERSORT algorithm. Additionally, single‐cell RNA sequencing (scRNA‐seq) data was used to further explicit the specific role and intercellular communications. Then receiver operating characteristic curves and least absolute shrinkage and selection operator were used to discover and test the potential diagnostic biomarkers for PAH. Both the immune cell infiltration analyses based on the microarray data sets and the cell proportion in scRNA‐seq data exhibited a significant downregulation in the infiltration of monocytes in PAH. Then, the intercellular communications showed that the interaction weighs of most immune cells, including monocytes changed between the control and PAH groups, and the ITGAL‐ITGB2 and ICAM signaling pathways played critical roles in this process. In addition, ITGAM and ICAM2 displayed good diagnosis values in PAH. This study implicated that the change of monocyte was one of the key immunologic features of PAH. Monocyte‐associated ICAM‐1 and ITGAL‐ITGB2 signaling pathways might be involved in the pathogenesis of PAH.
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