Targeting the NLRP3 inflammasome signalling for the management of atrial fibrillation.

IF 6.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY British Journal of Pharmacology Pub Date : 2024-06-15 DOI:10.1111/bph.16470
Alisha Niskala, Jordi Heijman, Dobromir Dobrev, Thomas Jespersen, Arnela Saljic
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Abstract

Inflammatory signalling via the nod-like receptor (NLR) family pyrin domain-containing protein-3 (NLRP3) inflammasome has recently been implicated in the pathophysiology of atrial fibrillation (AF). However, the precise role of the NLRP3 inflammasome in various cardiac cell types is poorly understood. Targeting components or products of the inflammasome and preventing their proinflammatory consequences may constitute novel therapeutic treatment strategies for AF. In this review, we summarise the current understanding of the role of the inflammasome in AF pathogenesis. We first review the NLRP3 inflammasome pathway and inflammatory signalling in cardiomyocytes, (myo)fibroblasts and immune cells, such as neutrophils, macrophages and monocytes. Because numerous compounds targeting NLRP3 signalling are currently in preclinical development, or undergoing clinical evaluation for other indications than AF, we subsequently review known therapeutics, such as colchicine and canakinumab, targeting the NLRP3 inflammasome and evaluate their potential for treating AF.

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针对 NLRP3 炎性体信号治疗心房颤动。
通过类点头受体(NLR)家族含吡啶结构域蛋白-3(NLRP3)炎性体发出的炎症信号最近被认为与心房颤动(房颤)的病理生理学有关。然而,人们对 NLRP3 炎性体在各种心脏细胞类型中的确切作用还知之甚少。靶向炎性体的成分或产物并防止其促炎后果可能构成心房颤动的新型治疗策略。在本综述中,我们总结了目前对炎性体在房颤发病机制中作用的理解。我们首先回顾了 NLRP3 炎性体通路以及心肌细胞、成纤维细胞和免疫细胞(如中性粒细胞、巨噬细胞和单核细胞)中的炎性信号传导。由于许多靶向 NLRP3 信号的化合物目前正处于临床前开发阶段,或正针对心房颤动以外的其他适应症进行临床评估,因此我们随后回顾了针对 NLRP3 炎症体的已知疗法,如秋水仙碱和卡那单抗,并评估了它们治疗心房颤动的潜力。
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来源期刊
CiteScore
15.40
自引率
12.30%
发文量
270
审稿时长
2.0 months
期刊介绍: The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries. Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues. In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.
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