转基因
医学
内科学
交感神经系统
心脏病学
交感神经节
心律失常
内分泌学
生物
转基因小鼠
细胞生物学
基因
遗传学
血压
心房颤动
作者
Rui Li,Ling Zhang,Peng Chen,Yanmei Lu,Zhihao Liu,Xiao Xu,Changyi Wang,Ran Hu,Wuping Tan,Liping Zhou,Yue-yi Wang,Lilei Yu,Yuhong Wang,Baopeng Tang,Hong Jiang
出处
期刊:Human Gene Therapy
[Mary Ann Liebert]
日期:2024-02-01
卷期号:35 (3-4): 114-122
摘要
The cardiac autonomic nervous system (CANS) is intimately connected to the regulation of electrophysiology and arrhythmogenesis in cardiac systems. This work aimed at investigating whether interleukin-10 (IL-10) could effectively modulate CANS and suppress ischemia-induced ventricular arrhythmia (VA) through chronically acting on the cardiac sympathetic ganglion (CSG). Using an adeno-associated virus (AAV), we achieved local chronic overproduction of IL-10 in the CSG, left stellate ganglion (LSG). As a result, in the IL-10 group, we observed a decreased number of tyrosine hydroxylase-positive (TH+) cells in the LSG. IL-10 markedly downregulated the nerve growth factor, synaptophysin, as well as growth-associated protein 43 expression. In vivo, results from ambulatory electrocardiography showed that IL-10 overexpression significantly inhibited the cardiac sympathetic nervous system activity and improved heart rate variability. Meanwhile, we observed decreased LSG function as well as prolonged ventricular effective refractory period and suppressed VA after myocardial infarction (MI) in the IL-10 group. In addition, IL-10 overexpression attenuated inflammation and decreased norepinephrine levels in the myocardium after acute MI. In conclusion, our data suggest that chronic IL-10 overexpression modulates cardiac sympathetic nerve remodeling and suppresses VA induced by MI. Neuromodulation through AAV-mediated IL-10 overexpression may have the characteristics of and advantages as a potential neuroimmunotherapy for preventing MI-induced VAs.
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