Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation
Background: The NRG1/ErbB4 signaling mechanism has been widely studied in the central nervous system for many years. However, the role of this pathway in modulating the intrinsic cardiac nervous system is largely unknown.Objective: The present study investigated whether the NRG1/ErbB4 signaling syst...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01082/full |
| _version_ | 1819155248421273600 |
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| author | Xiaoya Zhou Zhuo Wang Bing Huang Shenxu Yuan Xia Sheng Lilei Yu Guannan Meng Yuhong Wang Sunny S. Po Hong Jiang |
| author_facet | Xiaoya Zhou Zhuo Wang Bing Huang Shenxu Yuan Xia Sheng Lilei Yu Guannan Meng Yuhong Wang Sunny S. Po Hong Jiang |
| author_sort | Xiaoya Zhou |
| collection | DOAJ |
| description | Background: The NRG1/ErbB4 signaling mechanism has been widely studied in the central nervous system for many years. However, the role of this pathway in modulating the intrinsic cardiac nervous system is largely unknown.Objective: The present study investigated whether the NRG1/ErbB4 signaling system affects the activity of major atrial ganglionated plexi (GP) in a paroxysmal atrial fibrillation (AF) model by 6-h rapid atrial pacing (RAP).Methods: Twenty-four dogs were randomly divided into (1) a control group (saline microinjections into GP), (2) RAP group (saline microinjections into GP plus 6 h-RAP), (3) NRG1 group (microinjections of neuregulin-1 into GP plus 6 h-RAP) and (4) NRG1 + ERA group (microinjections of neuregulin-1 and ErbB4 receptor antagonist-ERA into GP plus 6 h-RAP). The effective refractory period (ERP), window of vulnerability (WOV), anterior right GP (ARGP) function and neural activity were measured. ARGP tissues were excised for histological study and western blotting.Results: When compared to the control group, 6 h-RAP produced a significant (1) decrease in ERP, an increase in ΣWOV, (2) an increase in ARGP neural activity and neural function, and (3) an increase in c-fos and nerve growth factor protein expression in the ARGP. However, microinjection of NRG1 into the ARGP prior to RAP prevented ERP shortening and AGRP activity enhancement and inhibited the expression of c-Fos and NGF proteins. Furthermore, these changes were significantly attenuated by pretreatment with an ErbB4 receptor antagonist.Conclusion: The NRG1/ErbB4 signaling pathway may exist in the GP, and activation of this pathway suppressed RAP-induced GP activation, atrial electrical remodeling and AF. |
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| language | English |
| last_indexed | 2024-12-22T15:33:57Z |
| publishDate | 2018-08-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-848d50db45ec4c77b7841c59fe9c8adb2022-12-21T18:21:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.01082376833Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial FibrillationXiaoya Zhou0Zhuo Wang1Bing Huang2Shenxu Yuan3Xia Sheng4Lilei Yu5Guannan Meng6Yuhong Wang7Sunny S. Po8Hong Jiang9Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaSir Run Run Shaw Institution of Clinical Medicine and Department of Cardiology, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHeart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United StatesDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaBackground: The NRG1/ErbB4 signaling mechanism has been widely studied in the central nervous system for many years. However, the role of this pathway in modulating the intrinsic cardiac nervous system is largely unknown.Objective: The present study investigated whether the NRG1/ErbB4 signaling system affects the activity of major atrial ganglionated plexi (GP) in a paroxysmal atrial fibrillation (AF) model by 6-h rapid atrial pacing (RAP).Methods: Twenty-four dogs were randomly divided into (1) a control group (saline microinjections into GP), (2) RAP group (saline microinjections into GP plus 6 h-RAP), (3) NRG1 group (microinjections of neuregulin-1 into GP plus 6 h-RAP) and (4) NRG1 + ERA group (microinjections of neuregulin-1 and ErbB4 receptor antagonist-ERA into GP plus 6 h-RAP). The effective refractory period (ERP), window of vulnerability (WOV), anterior right GP (ARGP) function and neural activity were measured. ARGP tissues were excised for histological study and western blotting.Results: When compared to the control group, 6 h-RAP produced a significant (1) decrease in ERP, an increase in ΣWOV, (2) an increase in ARGP neural activity and neural function, and (3) an increase in c-fos and nerve growth factor protein expression in the ARGP. However, microinjection of NRG1 into the ARGP prior to RAP prevented ERP shortening and AGRP activity enhancement and inhibited the expression of c-Fos and NGF proteins. Furthermore, these changes were significantly attenuated by pretreatment with an ErbB4 receptor antagonist.Conclusion: The NRG1/ErbB4 signaling pathway may exist in the GP, and activation of this pathway suppressed RAP-induced GP activation, atrial electrical remodeling and AF.https://www.frontiersin.org/article/10.3389/fphys.2018.01082/fullneuregulin-1ErbB4atrial fibrillationautonomic nervous systemganglionated plexi |
| spellingShingle | Xiaoya Zhou Zhuo Wang Bing Huang Shenxu Yuan Xia Sheng Lilei Yu Guannan Meng Yuhong Wang Sunny S. Po Hong Jiang Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation Frontiers in Physiology neuregulin-1 ErbB4 atrial fibrillation autonomic nervous system ganglionated plexi |
| title | Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation |
| title_full | Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation |
| title_fullStr | Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation |
| title_full_unstemmed | Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation |
| title_short | Regulation of the NRG1/ErbB4 Pathway in the Intrinsic Cardiac Nervous System Is a Potential Treatment for Atrial Fibrillation |
| title_sort | regulation of the nrg1 erbb4 pathway in the intrinsic cardiac nervous system is a potential treatment for atrial fibrillation |
| topic | neuregulin-1 ErbB4 atrial fibrillation autonomic nervous system ganglionated plexi |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01082/full |
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