Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Abstract

Background: Stanford type A aortic dissection (AAD) is a catastrophic disease. An immune infiltrate has been found within the aortic wall of dissected aortic specimens. The recall and activation of macrophages are key events in the early phases of AAD. Herein, the immune filtration profile of AAD was uncovered.Methods: Gene expression data from the GSE52093, GSE98770 and GSE153434 datasets were downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) of each dataset were calculated and then integrated. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the hub genes were identified in Cytoscape. Furthermore, gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of hub genes were performed. Finally, we set GSE52093 and GSE98770 as the training set and GSE153434 as the validation set to assess immune infiltration in AAD using CIBERSORTx and analyzed the correlations between immune cells and hub genes in both the training and validation sets.Results: Sixty-one integrated DEGs were identified. The top 10 hub genes were selected from the PPI network, and 140 biological process (BP) terms and 12 pathways were enriched among the top 10 hub genes. The proportions of monocytes and macrophages were significantly higher in AAD tissues than in normal tissues. Notably, this result was consistent in the training set and the validation set. In addition, we found that among the hub genes, CA9, CXCL5, GDF15, VEGFA, CCL20, HMOX1, and SPP1 were positively correlated with CD14, a cell marker of monocytes, while CA9, CXCL5, GDF15, and VEGFA were positively correlated with CD68, a cell marker of macrophages in the training set. Finally, according to the results of the GO and KEGG analysis of hub genes, we found that the monocyte/macrophage-related genes were involved in immune-inflammatory responses through degradation of the extracellular matrix, endothelial cell apoptosis, hypoxia and the interaction of cytokines and chemokines.Conclusion: The monocyte-macrophage system plays a major role in immune-inflammatory responses in the development of AAD. Several hub genes are involved in this process via diverse mechanisms.

Bioinformatics Analysis Reveals Cell Cycle-Related Gene Upregulation in Ascending Aortic Tissues From Murine Models

“…Much of the fundamental science of TAAD has focused on alterations in extracellular matrix components ( Grewal and Gittenberger-de Groot, 2018 ), smooth muscle function ( Rombouts, et al, 2021 ), and inflammation-related proteins ( Gao, et al, 2021 ). According to research over the past several decades, TAAD development is the result of complex changes in the vascular cellular and extracellular environment and not a simple degenerative process ( Del Porto, et al, 2013 ; He, et al, 2008 ; Malecki, et al, 2020 ; Sulkava, et al, 2017 ).…”

“…According to research over the past several decades, TAAD development is the result of complex changes in the vascular cellular and extracellular environment and not a simple degenerative process ( Del Porto, et al, 2013 ; He, et al, 2008 ; Malecki, et al, 2020 ; Sulkava, et al, 2017 ). To explore the molecular pathology of TAAD, many transcriptome sequences of TAAD samples from humans have been published, but these studies have had limitations ( Bi, et al, 2020 ; Fang, et al, 2021 ; Gao, et al, 2021 ). Control aortic samples are difficult to obtain from healthy human specimens, and there is a high degree of individual variation among human specimens.…”

“…Growing evidence suggests that inflammation participates in TAAD pathogenesis and the progression of disease ( Gao, et al, 2021 ; He, et al, 2008 ). Notably, inflammation may occur early in the disease and is thus a driving factor ( Goldfinger, et al, 2014 ; Wang, et al, 2021 ).…”

“…Gene expression analysis revealed upregulation of multiple inflammatory pathways related to programmed cell death. Macrophages are present in human TAAD samples and play a critical role in the pathogenesis of TAAD ( Del Porto, et al, 2013 ; Gao, et al, 2021 ). In our research, the inflammation-associated genes CD68, C1qa, and C3ar1 were hub genes.…”

Construction and Integrated Analysis of Competitive Endogenous Long Non-Coding RNA Network in Thoracic Aortic Dissection

“…5,21 Key KEGG pathways were highly enriched in cell cycle, mineral absorption, dilated cardiomyopathy, hypertrophic cardiomyopathy, and TNF signaling pathway, which were also in line with previous reports. [22][23][24] Three DEmRNAs were retained in the ceRNA network after screening. The expression of SLC7A5, which was consistent with the external dataset, was confirmed using qRT-PCR.…”