AUTHOR=Xia Meng , Wu Qingmeng , Chen Pengfei , Qian Cheng 

TITLE=Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.661709

DOI=10.3389/fcvm.2021.661709

ISSN=2297-055X

ABSTRACT=Background: Regulatory T cells (Tregs) has 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 CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using 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 DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory response, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte transendothelial migration, vascular smooth muscle contraction, and etc. 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 atherosclerosis progression, and facilitate the discovery of novel biomarkers for acute cardiovascular events.