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Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways
BACKGROUND: We previously demonstrated the gut microbes-derived metabolite trimethylamine N-oxide (TMAO) could activate the atrial autonomic ganglion plexus and promote atrial arrhythmia. The cardiac sympathetic nervous system (CSNS) play important roles in modulating ventricular arrhythmia (VA). ME...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603492/ https://www.ncbi.nlm.nih.gov/pubmed/30954457 http://dx.doi.org/10.1016/j.ebiom.2019.03.066 |
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author | Meng, Guannan Zhou, Xiaoya Wang, Menglong Zhou, Liping Wang, Zhenya Wang, Meng Deng, Jielin Wang, Yuhong Zhou, Zhen Zhang, Yifeng Lai, Yanqiu Zhang, Qianqian Yang, Xiaomeng Yu, Lilei Jiang, Hong |
author_facet | Meng, Guannan Zhou, Xiaoya Wang, Menglong Zhou, Liping Wang, Zhenya Wang, Meng Deng, Jielin Wang, Yuhong Zhou, Zhen Zhang, Yifeng Lai, Yanqiu Zhang, Qianqian Yang, Xiaomeng Yu, Lilei Jiang, Hong |
author_sort | Meng, Guannan |
collection | PubMed |
description | BACKGROUND: We previously demonstrated the gut microbes-derived metabolite trimethylamine N-oxide (TMAO) could activate the atrial autonomic ganglion plexus and promote atrial arrhythmia. The cardiac sympathetic nervous system (CSNS) play important roles in modulating ventricular arrhythmia (VA). METHODS: Part 1: To test whether TMAO can directly activate the CSNS, we performed local injection of TMAO into the left stellate ganglion (LSG). Part 2: To test whether TMAO can indirectly activate the CSNS through the central nervous system, we performed intravenous injection of TMAO. Ventricular electrophysiology and LSG function and neural activity were measured before and after TMAO administration. Then, the left anterior descending coronary artery was ligated, and electrocardiograms were recorded for 1 h. At the end of the experiment, LSG and paraventricular nucleus (PVN) tissues were excised for molecular analyses. FINDINGS: Compared with the control, both intravenous and local TMAO administration significantly increased LSG function and activity, shortened effective refractory period, and aggravated ischemia-induced VA. Proinflammatory markers and c-fos in the LSG were also significantly upregulated in both TMAO-treated groups. Particularly, c-fos expression in PVN was significantly increased in the systemic TMAO administration group but not the local TMAO administration group. INTERPRETATION: The gut microbe-derived metabolite TMAO can activate the CSNS and aggravate ischemia-induced VA via the direct pathway through the LSG and the indirect pathway through central autonomic activation. FUND: This work was supported by the National Key R&D Program of China [2017YFC1307800], and the National Natural Science Foundation of China [81530011, 81770364, 81570463, 81871486, 81600395, 81600367 and 81700444]. |
format | Online Article Text |
id | pubmed-6603492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-66034922019-07-12 Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways Meng, Guannan Zhou, Xiaoya Wang, Menglong Zhou, Liping Wang, Zhenya Wang, Meng Deng, Jielin Wang, Yuhong Zhou, Zhen Zhang, Yifeng Lai, Yanqiu Zhang, Qianqian Yang, Xiaomeng Yu, Lilei Jiang, Hong EBioMedicine Research paper BACKGROUND: We previously demonstrated the gut microbes-derived metabolite trimethylamine N-oxide (TMAO) could activate the atrial autonomic ganglion plexus and promote atrial arrhythmia. The cardiac sympathetic nervous system (CSNS) play important roles in modulating ventricular arrhythmia (VA). METHODS: Part 1: To test whether TMAO can directly activate the CSNS, we performed local injection of TMAO into the left stellate ganglion (LSG). Part 2: To test whether TMAO can indirectly activate the CSNS through the central nervous system, we performed intravenous injection of TMAO. Ventricular electrophysiology and LSG function and neural activity were measured before and after TMAO administration. Then, the left anterior descending coronary artery was ligated, and electrocardiograms were recorded for 1 h. At the end of the experiment, LSG and paraventricular nucleus (PVN) tissues were excised for molecular analyses. FINDINGS: Compared with the control, both intravenous and local TMAO administration significantly increased LSG function and activity, shortened effective refractory period, and aggravated ischemia-induced VA. Proinflammatory markers and c-fos in the LSG were also significantly upregulated in both TMAO-treated groups. Particularly, c-fos expression in PVN was significantly increased in the systemic TMAO administration group but not the local TMAO administration group. INTERPRETATION: The gut microbe-derived metabolite TMAO can activate the CSNS and aggravate ischemia-induced VA via the direct pathway through the LSG and the indirect pathway through central autonomic activation. FUND: This work was supported by the National Key R&D Program of China [2017YFC1307800], and the National Natural Science Foundation of China [81530011, 81770364, 81570463, 81871486, 81600395, 81600367 and 81700444]. Elsevier 2019-04-04 /pmc/articles/PMC6603492/ /pubmed/30954457 http://dx.doi.org/10.1016/j.ebiom.2019.03.066 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Meng, Guannan Zhou, Xiaoya Wang, Menglong Zhou, Liping Wang, Zhenya Wang, Meng Deng, Jielin Wang, Yuhong Zhou, Zhen Zhang, Yifeng Lai, Yanqiu Zhang, Qianqian Yang, Xiaomeng Yu, Lilei Jiang, Hong Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title_full | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title_fullStr | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title_full_unstemmed | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title_short | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
title_sort | gut microbe-derived metabolite trimethylamine n-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603492/ https://www.ncbi.nlm.nih.gov/pubmed/30954457 http://dx.doi.org/10.1016/j.ebiom.2019.03.066 |
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