Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis.

Xiaowen Tan,Xiaoxuan Tian,Lanlan Pan,Pengzhi Dong,Xiting Zhang

doi:10.1155/2017/4323496

Abstract

Background Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO), including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs) were analyzed. Results 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI) networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

Highlights

Atherosclerosis associated cardiovascular diseases (CVD) are the leading cause of mortality worldwide
Variety of inflammatory process was identified during atherosclerosis progression, which might be amenable to interventions
Functional annotation demonstrated that these Differentially expressed genes (DEGs) were mainly involved in osteoclast differentiation, cytokine-cytokine receptor interaction, chemokine signaling pathway, lysosome and Staphylococcus aureus infection, focal adhesion, regulation of actin cytoskeleton, arrhythmogenic right ventricular cardiomyopathy (ARVC), oxytocin signaling pathway, and cGMP-PKG signaling pathway

Summary

Introduction

Atherosclerosis associated cardiovascular diseases (CVD) are the leading cause of mortality worldwide. High-throughput platforms for analysis of gene expression, such as microarrays, are the promising tools for inferring biological relevancy, especially complex network during the process of atherosclerosis. Atherosclerotic gene expression profiling studies have been performed by microarray technology and suggested that hundreds of differentially expressed genes (DEGs) are involved in variety pathways, biological processes, or molecular functions. Microarray technology combined bioinformatics analysis made it possible to analyze the expression changes of mRNA from early to advanced stage of coronary atherosclerosis development, comprehensively. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis

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Discussion

Conclusion