肌肉肥大
上睑下垂
压力过载
医学
血管紧张素II
内科学
炎症体
纤维化
线粒体
心肌肥大
细胞生物学
内分泌学
血压
生物
炎症
作者
Jibo Han,Shanshan Dai,Lingfeng Zhong,Xiaowen Shi,Xiaoxi Fan,Xin Zhong,Wante Lin,Lan Su,Shuang Lin,Bingjiang Han,Jianjiang Xu,Hong Xia,Weijian Huang,Bozhi Ye
出处
期刊:Hypertension
[Ovid Technologies (Wolters Kluwer)]
日期:2022-11-01
卷期号:79 (11): 2505-2518
被引量:20
标识
DOI:10.1161/hypertensionaha.122.20004
摘要
Cardiac hypertrophy is initially an adaptive response of cardiomyocytes to neurohumoral or hemodynamic stimuli. Evidence indicates that Ang II (angiotensin II) or pressure overload causes GSDMD (gasdermin D) activation in cardiomyocytes and myocardial tissues. However, the direct impact of GSDMD on cardiac hypertrophy and its underlying mechanisms are not fully understood.In this study, we examined the aberrant activation of GSDMD in mouse and human hypertrophic myocardia, and the results showed that GSDMD deficiency reduced Ang II or pressure overload-induced cardiac hypertrophy, dysfunction, and associated cardiomyocyte pyroptosis in mice. Mechanistically, Ang II-mediated GSDMD cleavage caused mitochondrial dysfunction upstream of STING (stimulator of interferon genes) activation in vivo and in vitro. Activation of STING, in turn, potentiated GSDMD-mediated cardiac hypertrophy. Moreover, deficiency of both GSDMD and STING suppressed cardiac hypertrophy in cardiac-specific GSDMD-overexpressing mice.Based on these findings, we propose a mechanism by which GSDMD generates a self-amplifying, positive feed-forward loop with the mitochondria-STING axis. This finding points to the prospects of GSDMD as a key therapeutic target for hypertrophy-associated heart diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI