Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic Dysfunction

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-07-01 DOI:10.1016/j.jacbts.2025.02.004

Luge Li BS , Cristian Coarfa PhD , Yue Yuan MD, PhD , Issam Abu-Taha Dr sc hum , Xiaolei Wang PhD , Jia Song MD, MS , Yuying Zeng MS , Xiaohui Chen PhD , Amrit Koirala PhD , Sandra L. Grimm PhD , Markus Kamler MD , Lisa K. McClendon PhD , Michelle Tallquist PhD , Stanley Nattel MD , Dobromir Dobrev MD , Na Li PhD

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引用次数: 0

Abstract

Atrial fibrillation (AF) often coexists with heart failure, both involving inflammatory signaling and cardiac fibroblasts. To understand the role of fibroblast NLR family pyrin domain containing 3 (NLRP3) inflammasome in cardiac function, we found that NLRP3 was up-regulated in atrial fibroblasts from AF patients. Fibroblast-specific activation of NLRP3 in mice induced AF-promoting atrial myopathy and heart failure with diastolic dysfunction, accompanied by increased fibrosis, and reduced conduction velocity. Knockdown of NLRP3 prevented the AF-promoting atrial substrate and cardiomyopathy in the context of NLRP3 activation in fibroblasts. We identify the fibroblast NLRP3 inflammasome as a key pathway governing the promotion of proarrhythmic fibrosis in AF and cardiomyopathy.

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成纤维细胞限制性炎性小体激活促进心房颤动和心力衰竭伴舒张功能障碍。

心房颤动（AF）常与心力衰竭共存，两者均涉及炎症信号和心脏成纤维细胞。为了解成纤维细胞NLR家族pyrin domain containing 3 （NLRP3）炎性体在心功能中的作用，我们发现心房颤动患者的心房成纤维细胞中NLRP3表达上调。NLRP3在小鼠中的成纤维细胞特异性激活诱导af促进心房肌病和心力衰竭伴舒张功能障碍，并伴有纤维化增加和传导速度降低。在成纤维细胞中NLRP3激活的情况下，NLRP3的敲低可阻止af促进心房底物和心肌病。我们发现成纤维细胞NLRP3炎性体是AF和心肌病中促进心律失常纤维化的关键途径。

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.