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

Xiaogang Sun,Bowen Zhang,Shenghua Liang,Luchen Wang,Haoyu Gao,Yanxiang Liu,Jie Ren

doi:10.3389/fcvm.2021.680065

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.

Highlights

Aortic dissection is a catastrophic disease characterized by tears in the aortic wall
We found that among the hub genes, carbonic anhydrase 9 (CA9), CXCL5, growth differentiation factor 15 (GDF15), vascular endothelial growth factor A (VEGFA), C motif chemokine ligand 20 (CCL20), heme oxygenase 1 (HMOX1), and secreted phosphoprotein 1 (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
According to the results of the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (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

Summary

Introduction

Aortic dissection is a catastrophic disease characterized by tears in the aortic wall. AAD, which is defined as dissection involving the ascending aorta, carries a high risk of mortality and morbidity [1]. While type B dissections usually originate distal to the left subclavian artery and do not involve the ascending aorta. No effective drug therapy has been proven to control the development or progression of AAD, and the most valid strategy for AAD is open surgery, which has high technical requirements and must be performed in an experienced aortic center, which is a challenge for medically underdeveloped areas. Stanford type A aortic dissection (AAD) is a catastrophic disease. An immune infiltrate has been found within the aortic wall of dissected aortic specimens.

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Discussion

Conclusion