Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419302117 |
| _version_ | 1818293052099264512 |
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| author | Guannan Meng Xiaoya Zhou Menglong Wang Liping Zhou Zhenya Wang Meng Wang Jielin Deng Yuhong Wang Zhen Zhou Yifeng Zhang Yanqiu Lai Qianqian Zhang Xiaomeng Yang Lilei Yu Hong Jiang |
| author_facet | Guannan Meng Xiaoya Zhou Menglong Wang Liping Zhou Zhenya Wang Meng Wang Jielin Deng Yuhong Wang Zhen Zhou Yifeng Zhang Yanqiu Lai Qianqian Zhang Xiaomeng Yang Lilei Yu Hong Jiang |
| author_sort | Guannan Meng |
| collection | DOAJ |
| 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]. Keywords: Gut microbes, Trimethylamine N-oxide, Cardiac autonomic nervous system, Left stellate ganglion, Ventricular arrhythmia |
| first_indexed | 2024-12-13T03:09:43Z |
| format | Article |
| id | doaj.art-587a581572874896bf8b4dcaf23342de |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T03:09:43Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-587a581572874896bf8b4dcaf23342de2022-12-22T00:01:38ZengElsevierEBioMedicine2352-39642019-06-0144656664Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in contextGuannan Meng0Xiaoya Zhou1Menglong Wang2Liping Zhou3Zhenya Wang4Meng Wang5Jielin Deng6Yuhong Wang7Zhen Zhou8Yifeng Zhang9Yanqiu Lai10Qianqian Zhang11Xiaomeng Yang12Lilei Yu13Hong Jiang14Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, China; Corresponding authors at: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province 430060, China.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei, China; Hubei Key Laboratory of Cardiology, Wuhan, Hubei, China; Corresponding authors at: Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan City, Hubei Province 430060, China.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]. Keywords: Gut microbes, Trimethylamine N-oxide, Cardiac autonomic nervous system, Left stellate ganglion, Ventricular arrhythmiahttp://www.sciencedirect.com/science/article/pii/S2352396419302117 |
| spellingShingle | Guannan Meng Xiaoya Zhou Menglong Wang Liping Zhou Zhenya Wang Meng Wang Jielin Deng Yuhong Wang Zhen Zhou Yifeng Zhang Yanqiu Lai Qianqian Zhang Xiaomeng Yang Lilei Yu Hong Jiang Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context EBioMedicine |
| title | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context |
| title_full | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context |
| title_fullStr | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context |
| 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 pathwaysResearch in context |
| title_short | Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathwaysResearch in context |
| title_sort | gut microbe derived metabolite trimethylamine n oxide activates the cardiac autonomic nervous system and facilitates ischemia induced ventricular arrhythmia via two different pathwaysresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419302117 |
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