Exploring the causal links between inflammation-related genes and atherosclerosis through Mendelian randomization analysis.

Atherosclerosis is characterized by chronic inflammation and plaque formation in arterial walls, accompanying by significant involvement of immune cells and mediators. Studies have demonstrated that factors, such as colony-stimulating factor-1, play critical roles in the development and exacerbation of these plaques, emphasizing the complexity of immune interactions in atherosclerosis. This study utilized GSE198600, GSE120521, GSE253903, and GSE224273 datasets to investigate the gene expression profiles and molecular mechanisms underlying atherosclerotic plaques. Differentially expressed genes were identified using DESeq2, followed by pathway analysis with clusterProfiler. Key hub genes were further explored through Cytoscape, and Mendelian randomization was performed using the TwoSampleMR package to assess genetic causality using ebi-a-GCST005840 and ebi-a-GCST006907 datasets. Finally, single-cell RNA sequencing data from GSE224273 and GSE253903 datasets were analyzed to characterize gene expression across various cell types in carotid atherosclerotic lesions. This study presented a comprehensive analysis of gene expression across various cell types in carotid atherosclerosis, highlighting the significant roles of key genes such as HMOX1, CD52, CSF1R, CD177, PTGDS, and TNC. HMOX1, primarily expressed in macrophages and dendritic cells, played a pivotal role in the immune response within atherosclerotic environments. CD52 and CSF1R, exhibiting high expression in immune cells, were implicated in modulating inflammatory processes crucial for plaque development and stability. CD177 and PTGDS emerged as top differentially expressed genes in symptomatic carotid plaques, linking them to critical biological processes, such as immune response and prostaglandin synthesis, which are essential for atherosclerosis progression. Similarly, TNC, a gene associated with extracellular matrix organization, showed significant upregulation in unstable plaque sections, underscoring its potential role in plaque destabilization and adverse cardiovascular events. These findings elucidated the complex cellular and molecular interactions in atherosclerosis, providing insights into potential therapeutic targets for preventing or treating atherosclerotic cardiovascular diseases. The differential expression of these genes across various cell types further emphasized the heterogeneity of the disease and the need for targeted approaches to effectively manage atherosclerosis.