NLRP3缺乏介导的TAK1激活赋予心脏保护作用，抵抗压力超负荷诱导的心肌细胞焦亡和肥大。
TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.
作者信息
Li Xuan, You Jieyun, Dai Fangjie, Wang Shijun, Yang Feng Hua, Wang Xingxu, Ding Zhiwen, Huang Jiayuan, Chen Liming, Abudureyimu Miyesaier, Tang Haiyang, Yang Xiangdong, Xiang Yaozu, Backx Peter H, Ren Jun, Ge Junbo, Zou Yunzeng, Wu Jian
机构信息
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Cardiovascular Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
出版信息
JACC Basic Transl Sci. 2023 Aug 9;8(12):1555-1573. doi: 10.1016/j.jacbts.2023.05.008. eCollection 2023 Dec.
A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.
本研究全面阐述了NLRP3/半胱天冬酶-1/GSDMD介导的细胞焦亡在压力超负荷诱导的心肌肥大中的作用。此外，减轻NLRP3缺乏诱导的细胞焦亡可通过激活TAK1赋予心脏对压力超负荷的保护作用，而抑制TAK1活性则消除了这种有益作用，这突出了NLRP3-TAK1在调节炎症诱导的细胞死亡和肥大生长方面以前未被认识的相互调节作用。在转化医学方面，本研究表明基于炎症诱导的细胞死亡的策略可能在其他炎症和机械性超负荷疾病（如心肌梗死和二尖瓣反流）的治疗中得到应用。
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