Chronic Expression of Interleukin-10 Transgene Modulates Cardiac Sympathetic Ganglion Resulting in Reduced Ventricular Arrhythmia
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Human gene therapy - 35(2024), 3-4 vom: 21. Feb., Seite 114-122 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Rui [VerfasserIn] |
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| Links: |
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| Themen: |
130068-27-8 |
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| Anmerkungen: |
Date Completed 22.02.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1089/hum.2023.160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366219537 |
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| 520 | |a 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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| 700 | 1 | |a Zhang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yanmei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhihao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Changyi |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Ruijie |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Wuping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yueyi |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Lilei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Baopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Hong |e verfasserin |4 aut | |
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