Analysis of regulatory patterns of NLRP3 corpuscles and related genes and the role of macrophage polarization in atherosclerosis based on online database.

Our study examined the relationships and interactions among 30 genes related to the NOD-like receptor protein 3 (NLRP3) inflammasome. We identified 368 interconnections between these 30 genes, with NLRP3 participating in 38 interactions. The potential roles of these genes in atherosclerosis were evaluated based on protein-protein interaction networks and coexpression analysis. We identified differential expression in 20 genes, five of which were significantly upregulated: P2RX7, CASP1, CD36, GBP5, and PYCARD. We also observed a strong positive association between P2RX7 and PYCARD and as a notable negative association between RELA and CD36. Furthermore, our analysis revealed a clear association between the expression of inflammasome-associated genes and immune cell infiltration in disease specimens. To diagnose AS, a logistic regression model based on six inflammasome-related genes, achieved an Area under the curve of 0.996, indicating excellent diagnostic performance. Genomic enrichment analysis indicated that inflammasome-related genes were primarily involved in various pathways, such as hypertrophic cardiomyopathy and ribosomal function. To validate our findings, we confirmed the expression of risk genes in AS cells using qRT-PCR and Western blot techniques. Additionally, we observed a shift toward M2 polarization in THP-1 macrophages upon P2RX7 knockdown, further supporting our findings.