Abstract：
Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that the NLRP3 [NOD (nucleotide oligomerization domain)-, LRR (leucine-rich repeat)-, and PYD (pyrin domain)-containing protein 3] inflammasome is a key mediator in the development, progression, and destabilization of atherosclerotic plaques. This review aims to evaluate the current literature on the role of NLRP3 in human atherosclerosis. This systematic review was registered on the PROSPERO database (ID = CRD42022340039) and involved the search of a total of 8 databases. Records were screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies were included and quality assessed using the NIH: NHLBI tool. Six were eligible for meta-analysis using RevMan 5.4.1. We identified 20 relevant articles representing 3388 participants. NLRP3 mRNA levels and downstream cytokines, interleukin (IL)-1β and IL-18 were found to be associated with atherosclerotic disease. Fold changes in NLRP3 mRNA levels were most strongly associated with high risk atherosclerotic disease, compared to controls [0.84 (95 % CI: 0.41-1.28)]. IL-1β mRNA fold change was more robustly associated with high-risk atherosclerotic disease [0.61 (95 % CI: 0.10-1.13)] than IL-18 [0.47 (95 % CI: 0.02-0.91)]. NLRP3, IL-1β, and IL-18 are associated with high-risk atherosclerotic disease. However, given the scope of this review, the role of this inflammasome and its cytokine counterparts in acting as prognosticators of coronary artery disease severity is unclear. Several upstream activators such as cholesterol crystals are involved in the canonical or non-canonical activation of the NLRP3 inflammasome and its downstream cytokines. These findings highlight the necessity for further research to delineate the exact mechanisms of NLRP3 inflammasome activation and potential drug targets.
摘要：
动脉粥样硬化是一种慢性,以胆固醇在血管壁内沉积为特征的进行性心血管疾病。最近的文献表明，NLRP3[NOD（核苷酸寡聚化结构域）-，LRR（富含亮氨酸的重复序列）-，含PYD（Pyrin结构域）的蛋白3]炎性体是发育过程中的关键介质，programming,和动脉粥样硬化斑块的不稳定。本综述旨在评估NLRP3在人类动脉粥样硬化中的作用。该系统综述已在PROSPERO数据库（ID=CRD42022340039）上注册，并涉及总共8个数据库的搜索。根据系统评价和荟萃分析（PRISMA）指南的首选报告项目筛选记录。共纳入20项研究，并使用NIH：NHLBI工具进行质量评估。6人符合使用RevMan5.4.1进行荟萃分析的条件。我们确定了20篇相关文章，代表3388名参与者。NLRP3mRNA水平和下游细胞因子，研究发现白细胞介素(IL)-1β和IL-18与动脉粥样硬化疾病相关。NLRP3mRNA水平的倍数变化与高风险动脉粥样硬化疾病的相关性最强，与对照组相比[0.84（95%CI：0.41-1.28）]。与IL-18[0.47(95%CI:0.02-0.91)]相比，IL-1βmRNA倍数变化与高风险动脉粥样硬化疾病[0.61(95%CI:0.10-1.13)]的相关性更强。NLRP3，IL-1β，和IL-18与高风险动脉粥样硬化疾病相关。然而,鉴于本次审查的范围，这种炎症小体及其细胞因子在冠状动脉疾病严重程度的预测中的作用尚不清楚.几种上游活化剂如胆固醇晶体参与NLRP3炎性体及其下游细胞因子的规范或非规范活化。这些发现强调了进一步研究描述NLRP3炎性体激活的确切机制和潜在药物靶标的必要性。
