成纤维细胞特异性炎性小体激活促进心房颤动和舒张功能障碍性心力衰竭。

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

作者信息

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

机构信息

Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, Texas, USA.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.

出版信息

JACC Basic Transl Sci. 2025 Apr 16:101244. doi: 10.1016/j.jacbts.2025.02.004.

DOI:10.1016/j.jacbts.2025.02.004

PMID:40243956

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.

摘要

心房颤动（AF）常与心力衰竭并存，二者均涉及炎症信号传导和心脏成纤维细胞。为了解成纤维细胞含NLR家族吡啶结构域3（NLRP3）炎性小体在心脏功能中的作用，我们发现AF患者心房成纤维细胞中NLRP3上调。小鼠成纤维细胞特异性激活NLRP3可诱发促进AF的心房肌病和伴有舒张功能障碍的心力衰竭，同时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，敲低NLRP3可预防促进AF的心房基质和心肌病。我们确定成纤维细胞NLRP3炎性小体是控制AF和心肌病中促心律失常性纤维化的关键途径。