Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus

Meng Gao,Xiufen Qu,Dechun Yin,Jugang Chen

doi:10.1186/s12872-020-01363-x

Abstract

BackgroundMalignant 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.MethodsRats 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.ResultsAfter 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.ConclusionsIn 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.

Highlights

Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI)
While previous studies have demonstrated that other cytokines in the paraventricular nucleus (PVN), such as TNF-α and IL-1, play devastating roles, our study indicated that IL-6 in the PVN plays a protective role
In summary, the present study demonstrates that MI rats have higher concentrations of IL-6, Glycoprotein 130 (Gp130) and

Summary

Introduction

Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). 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. Lethal ventricular arrhythmia (VA) is the most common cause of death among patients with acute MI. It is well known that autonomic imbalance, especially excessive activation of sympathetic nerves (called a sympathetic storm), plays the most important role in promoting the occurrence of arrhythmia. There have been many reports on the mechanisms by which peripheral autonomic nerves, such as local cardiac nerves, renal sympathetic nerves, and star ganglions, regulate arrhythmia [3, 4]. The mechanism by which the central nervous system (CNS) affects VA remains unclear

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