Identification of key genes and pathways in atherosclerosis using integrated bioinformatics analysis

Abstract

Background Atherosclerosis (AS) is a chronic inflammatory disease that might induce severe cardiovascular events, such as myocardial infarction and cerebral infarction. These risk factors in the pathogenesis of AS remain uncertain and further research is needed. This study aims to explore the potential molecular mechanisms of AS by bioinformatics analyses. Methods GSE100927 gene expression profiles, including 69 AS samples and 35 healthy controls, were downloaded from Gene Expression Omnibus database and indenfied for key genes and pathways in AS. Results A total of 443 differentially expressed genes (DEGs) between control and AS were identified, including 323 down-regulated genes and 120 up-regulated genes. The Gene ontology terms enriched by the up-regulated DEGs were associated with the regulation of leukocyte activation, endocytic vesicle, and cytokine binding, while the down-regulated DEGs were associated with negative regulation of cell growth, extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis showed that the up-regulated DEGs were enriched in Osteoclast differentiation and Phagosome, while the down-regulated DEGs were enriched in vascular smooth muscle contraction and cGMP-PKG signaling pathway. Using the modular analysis of Cytoscape, we identified 3 modules mainly involved in Leishmaniasis and Osteoclast differentiation. The GSEA analysis showed the up-regulated gene sets were enriched in the ribosome, ascorbated metabolism, and propanoate metabolism. The LASSO Cox regression analysis showed the top 3 genes were TNF, CX3CR1, and COL1R1. Finally, we found these immune cells were conferred significantly higher infiltrating density in the AS group. Conclusions Our data showed the pathway of Osteoclast differentiation and Leishmaniasis was involved in the AS process and we developed a three-gene model base on the prognosis of AS. These findings clarified the gene regulatory network of AS and may provide a novel target for AS therapy.

Identification and validation of hub genes involved in foam cell formation and atherosclerosis development via bioinformatics

“…This also illustrates that numerous critical components, such as proteins, cytokines, and transcription factors, play a role in the disease’s development in the local microenvironment of atherogenesis ( Krauss, 2010 ; Napoli et al, 2012 ; Smith & Topol, 2006 ). When we analyzed the KEGG pathway enrichment of DEGs, we found that they were predominantly enriched in Osteoclast differentiation, B cell receptor signaling pathway, leukocyte transendothelial migration, and phagosome, most of which were activated by the development of atherosclerosis, a significant portion of this is triggered by the development of atherosclerosis ( Hemme et al, 2023 ; Li et al, 2023 ; Wang, Jiang & Cheng, 2022 ; Wang & Chen, 2022 ). Furthermore, the development of phagosomes plays a significant part in the production of foam cells ( Huynh, Gershenzon & Grinstein, 2008 ), and phagosome intervention may provide a possible support for foam cell reduction.…”

Online application for the diagnosis of atherosclerosis by six genes

“…Rong et al identified six core genes linked to atherosclerotic plaque progression in the protein-protein interaction (PPI) network [ 24 ]. Shihuan et al developed a three-gene model to evaluate the prognosis of AS [ 25 ]. Yajuan et al identified three critical genes diagnostic biomarkers of AS [ 26 ].…”