中国病理生理杂志2025,Vol.41Issue(4):661-668,8.DOI:10.3969/j.issn.1000-4718.2025.04.005
NLRC3在血管内皮细胞中的功能初探及在冠心病中的诊断价值
Function of NLRC3 in endothelial cells and its diagnostic significance in coronary artery disease
摘要
Abstract
AIM:To investigate the role of NLR family CARD domain containing 3(NLRC3)in endothelial cells and evaluate its diagnostic value in coronary artery disease.METHODS:Twenty male ApoE-/-C57BL/6 mice,aged eight weeks,were randomly assigned into two groups:an experimental group and a control group,with each group com-prising ten mice.The experimental group was subjected to a high-fat diet for 8 weeks to induce atherosclerosis(AS),whereas the control group was maintained on a standard diet.The expression of NLRC3 in the aorta was evaluated using RT-qPCR and immunofluorescence techniques.Additionally,human umbilical vein endothelial cells(HUVECs)were ex-posed to interleukin-1β(IL-1β)to investigate the expression levels of NLRC3.Lentiviral vectors or plasmid vectors were employed to either overexpress or knock down NLRC3 in endothelial cells,and subsequently subjected to inflammation in-duced by IL-1β.The RT-qPCR and ELISA were employed to assess the impact of NLRC3 on inflammation in endothelial cells.Western blot and immunofluorescence techniques were utilized to investigate the modulation of the NF-κB signaling pathway in endothelial cells by NLRC3.Plasma NLRC3 levels in coronary artery disease patients and healthy controls were measured using ELISA,and its diagnostic potential was assessed through ROC curve analysis.RESULTS:In AS mice,distinct plaque lesions were observed in the aorta,accompanied by a significantly reduced expression of NLRC3 in the aortic arch relative to the control group.Expression of NLRC3 exhibited a significant down-regulation in IL-1β-stimu-lated HUVECs,demonstrating both time-dependent and dose-dependent effects(P<0.01).Overexpression of NLRC3 markedly suppressed the levels of IL-6,IL-8,monocyte chemoatbactant protein-1(MCP-1),p-p65,and p-IκBα in endo-thelial cells stimulated with IL-1β(P<0.01).Conversely,knockdown of NLRC3 resulted in elevated levels of IL-6,IL-8,MCP-1,p-p65 and p-IκBα in endothelial cells(P<0.01).Coronary artery disease patients had significantly lower plasma NLRC3 levels than controls,with an AUC of 0.851(95%CI:0.785~0.918,P<0.01).A diagnostic threshold of 1.605 µg/L yielded a sensitivity of 93.8%and a specificity of 71.3%.CONCLUSION:The NLRC3 may modulate endothelial inflammation and suppress AS progression through inhibition of the NF-κB signaling pathway,and it holds potential as a diagnostic biomarker for coronary artery disease.关键词
NLR家族含CARD域蛋白3/内皮细胞/炎症/冠心病/NF-κB信号通路Key words
NLR family CARD domain containing 3/endothelial cells/inflammation/coronary artery dis-ease/NF-κB signaling pathway分类
医药卫生引用本文复制引用
古晓东,翁锐强,赵俊丽,李霞,刘苏东..NLRC3在血管内皮细胞中的功能初探及在冠心病中的诊断价值[J].中国病理生理杂志,2025,41(4):661-668,8.基金项目
广东省基础与应用基础研究基金企业联合基金面上项目(No.2024A1515220103) (No.2024A1515220103)
广东省基础与应用基础研究基金面上项目(No.2024A1515010809) (No.2024A1515010809)
梅州市社会发展科技计划项目(No.2023B04) (No.2023B04)