TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy

作者：Xuan Li, Jieyun You, Fangjie Dai, Shijun Wang, Feng Hua Yang, Xingxu Wang, Zhiwen Ding, Jiayuan Huang, Liming Chen, Miyesaier Abudureyimu, Haiyang Tang, Xiangdong Yang, Yaozu Xiang, Peter H. Backx, Jun Ren, Junbo Ge, Yunzeng Zou, Jian Wu · 发表于：JACC Basic to Translational Science · 年份：2023 · DOI：10.1016/j.jacbts.2023.05.008 · 被引用次数：19 · 研究领域：Inflammasome and immune disorders、Cardiac Fibrosis and Remodeling、Cardiovascular Effects of Exercise

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.