Investigation of the Underlying Genes and Mechanism of Macrophage-Enriched Ruptured Atherosclerotic Plaques Using Bioinformatics Method

• Published in: Journal of Atherosclerosis and Thrombosis 2019/07/01, Vol.26(7), pp.636-658
• Main Authors: Wang, Hao, Liu, Dongyuan, Zhang, Hongbing
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Differentially Expressed Genes; Macrophages; microRNA; Original; Ruptured atherosclerotic plaque; Transcription factors
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.45963

Aim: The study aimed to identify the underlying differentially expressed genes (DEGs) and mechanism of macrophage-enriched rupture atherosclerotic plaque using bioinformatics methods.Methods: GSE41571, which includes six stable samples and five ruptured atherosclerotic samples, was downloaded from the GEO database. After preprocessing, DEGs between ruptured and stable atherosclerotic samples were identified using LIMMA. Gene Ontology biological process (GO_BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using the Database for Annotation, Visualization, and Integration Discovery (DAVID) online tool. Based on the STRING database, protein-protein interactions (PPIs) network among DEGs were constructed. Regulatory relationships between miRNAs/transcriptional factors (TFs) and target genes were predicted using Enrichr, and regulatory networks were visualized using Cytoscape.Results: A total of 268 DEGs (64 up-regulated and 204 down-regulated DEGs) were identified between ruptured and stable samples. In the PPI network, collagen type III alpha 1 chain (COL3A1), collagen type I alpha 2 chain (COL1A2), and asporin (ASPN) were more than 15 interaction degrees. In the miRNA-target network, miR21 was highlighted with highest degrees and ASPN could be targeted by miR21. Functional enrichment analysis showed that COL3A1 and COL1A2 were significantly enriched in extracellular matrix organization and cell adhesion GO_BP terms. Pre-platelet basic protein (PPBP) was the most significantly up-regulated gene in ruptured atherosclerotic samples and enriched in immune response and inflammatory response GO_BP terms. Conclusions: Down-regulated COL3A1, COL1A2 and ASPN, and up-regulated PPBP might perform critical promotional roles in atherosclerotic plaque rupture. Furthermore, miR21 might be potential target to prevent atherosclerotic rupture.