Immune-Related Genes in the Pathogenesis of Atherosclerosis: Based on Sex Differences.

Abstract

Atherosclerosis is still a global public problem with increasing incidence rate and mortality. It has been found that gender factors play an important role in the progression of atherosclerosis. However, few people explore gender related atherosclerosis at the level of genes and immune cells. The purpose of this study was to determine genetic and immune cell differences between male and female samples. This study aims to identify differential genes between male and female samples in the GSE43292 dataset. The focus will be on identifying immune-related genes (IRGs) among these differentially expressed genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis will be employed to explore the enrichment of IRGs in biological processes, molecular functions, cellular components, and pathways. Furthermore, a protein-protein interaction (PPI) network for the IRGs will be constructed using Cytoscape software. To estimate the degree of immune cell infiltration, single-sample gene set enrichment analysis (ssGSEA) will be conducted. Moreover, the identified IRGs will be validated using GSE28829 dataset. Finally, we validated in atherosclerotic mice. Seven IRGs (CCL13, IL1RN, FPR2, S100A8, CCL19, CXCL1, CXCL8) were identified as being overexpressed in male atherosclerosis. GO and KEGG analysis revealed that these IRGs are primarily enriched in inflammatory response pathways, cytokine signaling pathways, and cytokine- cytokine receptor interactions. Notably, when compared to females, there was a significant infiltration of immune cells in male specimens. Importantly, all seven IRGs demonstrated high diagnostic value in GSE28829 dataset. The use of animal samples supports our results. This study demonstrates the effectiveness of seven IRGs and reveal sex differences in atherosclerosis. Notably, there is a significant presence of immune cells within the atherosclerotic plaque of men compared to women. These findings have potential implications for the development of personalized treatment approaches targeting gender-related atherosclerosis.