Inhibition of Satellite Glial Cell Activation in Stellate Ganglia Prevents Ventricular Arrhythmogenesis and Remodeling After Myocardial Infarction

作者：Zhen Zhou, Hanyu Zhang, Hongbo Xiong, Ke‐Qiong Deng, Meng Zheng, Yongkang Zhang, Zhendong Xu, Ruifeng Tian, Tong Zhang, Xiangjie Kong, Yingying Hu, Yinhua Luo, Huanhuan Cai, Di Fan, Qing Wang, Bo He, Qiongxin Wang, Zhibing Lu · 发表于：Circulation Arrhythmia and Electrophysiology · 年份：2025 · DOI：10.1161/circep.125.013866 · 被引用次数：7 · 研究领域：Vagus Nerve Stimulation Research、Cardiac electrophysiology and arrhythmias、Neuroscience of respiration and sleep

BACKGROUND: Hyperactivity of sympathetic neurons in the stellate ganglia (SG) contributes to ventricular arrhythmias and remodeling postmyocardial infarction (MI). However, the role of satellite glial cells (SGCs) surrounding the neurons in this process remains unknown. METHODS: SGC-specific chemogenetic manipulation was locally applied to modulate SG-SGC activity dual-directionally in the rats with naïve or infarcted hearts. Subsequently, cardiac sympathetic neural activity and ventricular electrophysiological stability in response to stimulation were evaluated, as well as cardiac neural and structural remodeling post-MI. SG bulk RNA sequencing and the interaction between SGCs and sympathetic neurons isolated from SG were used to explore the underpinning mechanisms. RESULTS: SG-SGC excitation increased SG neural activity and ventricular electrophysiological instability in rats with naïve hearts, whereas its inhibition influenced none of the above under physiological conditions. Of note, 2-hour-MI provoked SG-SGC activation that positively correlated with cardiac sympathetic neurotransmitter (norepinephrine) release. Accordingly, SGC activation in the SG enhanced cardiac sympathetic hyperactivity 2 hours post-MI, whereas SG-SGC inhibition suppressed MI-induced cardiac sympathetic hyperexcitability. Moreover, the persistent inhibition of SG-SGCs improved ventricular remodeling and dysfunction, alleviated SG and ventricular sympathetic nerve sprouting 7 days post-MI. In additio...