Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus
Abstract Background Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incomp...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-02-01
|
Series: | BMC Cardiovascular Disorders |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12872-020-01363-x |
_version_ | 1818872518158581760 |
---|---|
author | Meng Gao Dechun Yin Jugang Chen Xiufen Qu |
author_facet | Meng Gao Dechun Yin Jugang Chen Xiufen Qu |
author_sort | Meng Gao |
collection | DOAJ |
description | Abstract Background Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incompletely understood. In this study, we investigated changes in the interleukin-6 (IL-6)-glycoprotein 130-signal transducer and activator of transcription 3 (STAT3) pathway in the PVN during acute MI and the effects of this pathway on ventricular stability. Methods Rats were divided into a control group, a MI group, a PVN-injected anti-IL-6 antibody group and a PVN-injected SC144 group to observe how IL-6 and its downstream glycoprotein 130-STAT3 pathway in the PVN affect ventricular stability. The left anterior descending coronary artery was ligated to induce MI. After that, an anti-IL-6 antibody and SC144 were injected into the PVNs of rats. All data are expressed as the mean ± SE and were analysed by ANOVA with a post hoc LSD test. p < 0.05 was considered to indicate statistical significance. Results After MI, the concentration of the inflammatory factor IL-6 increased, and its downstream glycoprotein 130-STAT3 pathway was activated in the PVN. After injection of MI rat PVNs with the anti-IL-6 antibody or glycoprotein 130 inhibitor (SC144), glutamate levels increased and γ-aminobutyric acid (GABA) levels decreased in the PVN. Plasma norepinephrine concentrations also increased after treatment, which increased the vulnerability to VA. Conclusions In summary, IL-6 in the PVN exerts a protective effect in MI rats, and the glycoprotein 130-STAT3 pathway plays a key role in this process. We anticipate that our findings will provide new ideas for the prevention and treatment of arrhythmia after MI. |
first_indexed | 2024-12-19T12:40:05Z |
format | Article |
id | doaj.art-34e6fd4ba46e49d1868a0992e83edbcb |
institution | Directory Open Access Journal |
issn | 1471-2261 |
language | English |
last_indexed | 2024-12-19T12:40:05Z |
publishDate | 2020-02-01 |
publisher | BMC |
record_format | Article |
series | BMC Cardiovascular Disorders |
spelling | doaj.art-34e6fd4ba46e49d1868a0992e83edbcb2022-12-21T20:21:00ZengBMCBMC Cardiovascular Disorders1471-22612020-02-012011910.1186/s12872-020-01363-xActivating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleusMeng Gao0Dechun Yin1Jugang Chen2Xiufen Qu3Department of Cardiology, the First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, the First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, the First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, the First Affiliated Hospital of Harbin Medical UniversityAbstract Background Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incompletely understood. In this study, we investigated changes in the interleukin-6 (IL-6)-glycoprotein 130-signal transducer and activator of transcription 3 (STAT3) pathway in the PVN during acute MI and the effects of this pathway on ventricular stability. Methods Rats were divided into a control group, a MI group, a PVN-injected anti-IL-6 antibody group and a PVN-injected SC144 group to observe how IL-6 and its downstream glycoprotein 130-STAT3 pathway in the PVN affect ventricular stability. The left anterior descending coronary artery was ligated to induce MI. After that, an anti-IL-6 antibody and SC144 were injected into the PVNs of rats. All data are expressed as the mean ± SE and were analysed by ANOVA with a post hoc LSD test. p < 0.05 was considered to indicate statistical significance. Results After MI, the concentration of the inflammatory factor IL-6 increased, and its downstream glycoprotein 130-STAT3 pathway was activated in the PVN. After injection of MI rat PVNs with the anti-IL-6 antibody or glycoprotein 130 inhibitor (SC144), glutamate levels increased and γ-aminobutyric acid (GABA) levels decreased in the PVN. Plasma norepinephrine concentrations also increased after treatment, which increased the vulnerability to VA. Conclusions In summary, IL-6 in the PVN exerts a protective effect in MI rats, and the glycoprotein 130-STAT3 pathway plays a key role in this process. We anticipate that our findings will provide new ideas for the prevention and treatment of arrhythmia after MI.https://doi.org/10.1186/s12872-020-01363-xHypothalamic paraventricular nucleusInterleukin-6Glycoprotein 130STAT3Sympathetic activityCardiac electrophysiological activity |
spellingShingle | Meng Gao Dechun Yin Jugang Chen Xiufen Qu Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus BMC Cardiovascular Disorders Hypothalamic paraventricular nucleus Interleukin-6 Glycoprotein 130 STAT3 Sympathetic activity Cardiac electrophysiological activity |
title | Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
title_full | Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
title_fullStr | Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
title_full_unstemmed | Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
title_short | Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
title_sort | activating the interleukin 6 gp130 stat3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus |
topic | Hypothalamic paraventricular nucleus Interleukin-6 Glycoprotein 130 STAT3 Sympathetic activity Cardiac electrophysiological activity |
url | https://doi.org/10.1186/s12872-020-01363-x |
work_keys_str_mv | AT menggao activatingtheinterleukin6gp130stat3pathwayamelioratesventricularelectricalstabilityinmyocardialinfarctionratsbymodulatingneurotransmittersintheparaventricularnucleus AT dechunyin activatingtheinterleukin6gp130stat3pathwayamelioratesventricularelectricalstabilityinmyocardialinfarctionratsbymodulatingneurotransmittersintheparaventricularnucleus AT jugangchen activatingtheinterleukin6gp130stat3pathwayamelioratesventricularelectricalstabilityinmyocardialinfarctionratsbymodulatingneurotransmittersintheparaventricularnucleus AT xiufenqu activatingtheinterleukin6gp130stat3pathwayamelioratesventricularelectricalstabilityinmyocardialinfarctionratsbymodulatingneurotransmittersintheparaventricularnucleus |