Shen Wen, Wu Tao, Liu Qiang, Ke Ben
Department of Cardiovascular Medicne, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Nanchang, 330006, P.R. China.
Department of Cardiovascular Medicne, Jiangxi Provincial People's Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, P.R. China.
Mol Genet Genomics. 2024 Dec 27;300(1):7. doi: 10.1007/s00438-024-02216-4.
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.
我们的研究检测了与NOD样受体蛋白3（NLRP3）炎性小体相关的30个基因之间的关系和相互作用。我们确定了这30个基因之间的368个相互联系，其中NLRP3参与了38个相互作用。基于蛋白质-蛋白质相互作用网络和共表达分析评估了这些基因在动脉粥样硬化中的潜在作用。我们确定了20个基因存在差异表达，其中5个显著上调：P2RX7、CASP1、CD36、GBP5和PYCARD。我们还观察到P2RX7与PYCARD之间存在强正相关，而RELA与CD36之间存在显著负相关。此外，我们的分析揭示了炎性小体相关基因的表达与疾病标本中免疫细胞浸润之间存在明显关联。为了诊断动脉粥样硬化（AS），基于六个炎性小体相关基因的逻辑回归模型的曲线下面积达到0.996，表明具有出色的诊断性能。基因组富集分析表明，炎性小体相关基因主要参与各种途径，如肥厚型心肌病和核糖体功能。为了验证我们的发现，我们使用qRT-PCR和蛋白质免疫印迹技术在AS细胞中证实了风险基因的表达。此外，我们观察到在敲低P2RX7后，THP-1巨噬细胞向M2极化转变，进一步支持了我们的发现。
