Marina Khair MBBS , Mark Khair BSc , Venkat N. Vangaveti PhD , Usman H. Malabu MBBS, MSc
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引用次数: 0
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.
期刊介绍：
The official journal of the Japanese College of Cardiology is an international, English language, peer-reviewed journal publishing the latest findings in cardiovascular medicine. Journal of Cardiology (JC) aims to publish the highest-quality material covering original basic and clinical research on all aspects of cardiovascular disease. Topics covered include ischemic heart disease, cardiomyopathy, valvular heart disease, vascular disease, hypertension, arrhythmia, congenital heart disease, pharmacological and non-pharmacological treatment, new diagnostic techniques, and cardiovascular imaging. JC also publishes a selection of review articles, clinical trials, short communications, and important messages and letters to the editor.
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