فهرست نشریات علمی دسترسی آزاد ایران

Background and Objectives: Atherosclerosis (AS) is a major cause of cardiovascular disease with complex immune-mediated pathogenesis. This study aimed to identify hub immune-related genes involved in AS and investigate their causal mechanisms using comprehensive bioinformatics and experimental approaches.   Methods: Differentially expressed immune-related genes (DE-IRGs) were identified from GSE20129 dataset (48 AS, 71 controls) using bioinformatics analysis (|log2 fold change| > 1.0, adjusted p-value < 0.05). Functional enrichment, protein-protein interaction network analysis, and immune cell infiltration analysis were performed. A nomogram model for AS risk prediction was developed and validated internally. Mendelian randomization (MR) analysis explored causal relationships between hub genes and AS. STAT1 function was experimentally validated using siRNA knockdown in RAW264.7 cells treated with LPS (100 ng/mL, 24h) followed by qPCR, migration, and cytokine assays.   Results: We identified 125 DE-IRGs primarily involved in cytokine signaling and leukocyte functions. Ten hub DE-IRGs were identified, with STAT1 having the highest connectivity. The nomogram model demonstrated good predictive performance (calibration curve with minimal deviation). MR analysis revealed a potential causal relationship between STAT1 levels and AS susceptibility (OR=0.916, 95%CI=0.835-1.004, P=0.042). Experimental validation showed STAT1 knockdown significantly reduced LPS-induced inflammatory cytokine production and macrophage migration.   Conclusion: This study provides valuable insights into the molecular pathogenesis of AS through integrated bioinformatics, MR analysis, and experimental validation. The identified hub genes, particularly STAT1, represent promising candidates for targeted interventions in AS management and prevention.