Cardiomyocyte Inflammasome Signaling in Cardiomyopathies and Atrial Fibrillation: Mechanisms and Potential Therapeutic Implications.

Cardiomyocyte Inflammasome Signaling in Cardiomyopathies and Atrial Fibrillation: Mechanisms and Potential Therapeutic Implications.
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DOI:
10.3389/fphys.2018.01115
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发表时间:
2018
影响因子:
4
通讯作者:
Li N
Li N
中科院分区:
医学2区
文献类型:
--
作者:
Chen G;Chelu MG;Dobrev D;Li N

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炎性小体是免疫细胞和其他细胞的胞质溶胶中的高分子量蛋白质复合物,其在响应细胞应激的先天免疫系统中起关键作用。NLRP 3炎性体是最了解的炎性体,已知其介导半胱天冬酶-1从半胱天冬酶原-1成熟(活化),引起细胞因子(例如,白细胞介素-1 β),并可能导致一种称为焦亡的炎性程序性细胞死亡。以前的工作表明,NLRP 3组分在心肌细胞和心脏成纤维细胞中表达,最近的研究已经确定NLRP 3炎性小体是心肌病和心房颤动发病机制中的关键节点,这可能为开发新的治疗药物创造机会。在这里,我们回顾了最近的证据NLRP 3炎性小体在心肌细胞中的作用,并讨论了其在心脏重塑和心律失常的演变中的潜在作用,以及这些最新的发展所创造的新机会。
Inflammasomes are high molecular weight protein complexes in the cytosol of immune and other cells that play a critical role in the innate immune system in response to cellular stress. NLRP3 inflammasome, the best-understood inflammasome, is known to mediate the maturation (activation) of caspase-1 from pro-caspase-1, causing the maturation and release of cytokines (e.g., interleukin-1β) and potentially leading to a form of inflammatory programmed cell death called pyroptosis. Previous work has shown that the NLRP3 components are expressed in cardiomyocytes and cardiac fibroblasts and recent studies have identified the NLRP3 inflammasome as a key nodal point in the pathogenesis of cardiomyopathies and atrial fibrillation, which may create an opportunity for the development of new therapeutic agents. Here we review the recent evidence for a role of NLRP3 inflammasome in the cardiomyocytes and discuss its potential role in the evolution of cardiac remodeling and arrhythmias and new opportunities created by these very recent developments.
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