Six-Gene Signature Associated with Immune Cells in the Progression of Atherosclerosis Discovered by Comprehensive Bioinformatics Analyses

Abstract

Background. As a multifaceted disease, atherosclerosis is often characterized by the formation and accumulation of plaque anchored to the inner wall of the arteries and causes some cardiovascular diseases and vascular embolism. Numerous studies have reported on the pathogenesis of atherosclerosis. However, fewer studies focused on both genes and immune cells, and the correlation of genes and immune cells was evaluated via comprehensive bioinformatics analyses. Methods. 29 samples of atherosclerosis-related gene expression profiling, including 16 human advanced atherosclerosis plaque (AA) and 13 human early atherosclerosis plaque (EA) samples from the Gene Expression Omnibus (GEO) database, were analyzed to get differentially expressed genes (DEGs) and the construction of protein and protein interaction (PPI) networks. Besides, we detected the relative fraction of 22 immune cell types in atherosclerosis by using the deconvolution algorithm of “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT).” Ultimately, based on the significantly changed types of immune cells, we executed the correlation analysis between DEGs and immune cells to discover the potential genes and pathways associated with immune cells. Results. We identified 17 module genes and 6 types of significantly changed immune cells. Correlation analysis showed that the relative percentage of T cell CD8 has negative correlation with the C1QB expression (R=−0.63, p=0.02), and the relative percentage of macrophage M2 has positive correlation with the CD86 expression (R=0.57, p=0.041) in EA. Meanwhile, four gene expressions (CD53, C1QC, NCF2, and ITGAM) have a high correlation with the percentages of T cell CD8 and macrophages (M0 and M2) in AA samples. Conclusions. In this study, we suggested that the progression of atherosclerosis might be related to CD86, C1QB, CD53, C1QC, NCF2, and ITGAM and that it plays a role in regulating immune-competent cells such as T cell CD8 and macrophages M0 and M2. These results will enable studies of the potential genes associated with immune cells in the progression of atherosclerosis, as well as provide insight for discovering new treatments and drugs.

Identification of Potential Key Genes Involved in the Carotid Atherosclerosis

“… 29 The progression of carotid atherosclerosis is related to CD53. 30 In the present study, the aim was to focus on DEGs between atheroma plaque and control samples. However, due to lack of experimental validation, it is not clear whether these genes are causal or merely markers.…”

Differentially Expressed Genes and Enriched Signaling Pathways in the Adipose Tissue of Obese People

“…It is mainly expressed on the membranes of immune cells, where it helps regulate many of their functions, including adhesion, migration, and cell fusion ( Dunlock, 2020 ), and plays an important role in antigen presentation. Many studies have shown that CD53 is increased in obese and inflammatory tissues, and regulating its expression may be an effective treatment for obesity with complications ( Nair et al, 2005 ; Zhao et al, 2020 ). PLEK is the major protein kinase C substrate phosphorylated in diabetic macrophages, where a 30% reduction in PLEK can inhibit TNFα secretion by 80% ( Ding et al, 2007 ).…”

Targeting cytokines and immune checkpoints in atherosclerosis with monoclonal antibodies

“…Overexpression of the co-inhibitory CTLA4 reduced atherosclerotic burden and plaque inflammation in Apoe − /− mice and resulted in a profound decrease in effector T cells [107]. In human atherosclerotic plaques, expression of CD80/CD86 is correlated with plaque vulnerability [108], and a recent bioinformatics study identified CD86 as one out of 6 genes driving immune cell activation in human atherosclerosis [109] . Patients suffering from coronary artery disease and those at risk of stroke displayed an increased expression of CD80 and CD86 on monocyte-derived DCs and B cells [110].…”