Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis
Meng Xia, Qingmeng Wu, Pengfei Chen, Cheng Qian
Abstract
Background: Regulatory T cells (Tregs) have shown to be protective against the development of atherosclerosis, a major pathological cause for cardiovascular events. Here, we aim to explore the roles of Tregs-related genes in atherosclerosis deterioration. Methods and Results: We downloaded the gene expression profile of 29 atherosclerotic samples from the Gene Expression Omnibus database with an accession number of GSE28829 . The abundance of Tregs estimated by the CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using the limma test and correlation analysis, a total of 159 differentially expressed Tregs-related genes (DETregRGs) between early and advanced atherosclerotic plaques were documented. Functional annotation analysis using the DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory responses, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte trans-endothelial migration, vascular smooth muscle contraction, and so on. A protein-protein interaction network of the DETregRGs was then constructed, and five hub genes ( PTPRC, C3AR1, CD53, TLR2 , and CCR1 ) were derived from the network with node degrees ≥20. The expression patterns of these hub DETregRGs were further validated in several independent datasets. Finally, a single sample scoring method was used to build a gene signature for the five DETregRGs, which could distinguish patients with myocardial infarction from those with stable coronary disease. Conclusion: The results of this study will improve our understanding about the Tregs-associated molecular mechanisms in the progression of atherosclerosis and facilitate the discovery of novel biomarkers for acute cardiovascular events.