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Sympathetic nerve blocks promote anti-inflammatory response by activating the JAK2-STAT3-mediated signaling cascade in rat myocarditis models: A novel mechanism with clinical implications

 Hyelim Park  ;  Hyewon Park  ;  Dasom Mun  ;  Michael Kim  ;  Hui-Nam Pak  ;  Moon-Hyoung Lee  ;  Boyoung Joung 
 HEART RHYTHM, Vol.15(5) : 770-779, 2018 
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Anti-inflammatory ; Arrhythmia ; Cholinergic ; JAK2-STAT3-mediated signaling ; Stellectomy
BACKGROUND: Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses. OBJECTIVE: The purpose of this study was to evaluate the effect of left stellectomy on CAIP using rat experimental autoimmune myocarditis (EAM) models. METHODS: EAM was produced by injecting 2 mg of porcine cardiac myosin into the footpads of rats. Left stellectomy was performed before EAM induction. We evaluated the effect of left stellectomy on arrhythmic events, survival, inflammation, and CAIP in rats without and with EAM. RESULTS: Left stellectomy prevented arrhythmia and improved survival in EAM rats. Left stellectomy decreased the levels of tumor necrosis factor alpha, interleukin 6, and high mobility group box 1 (P < .05 vs EAM) in serum and heart tissues from EAM rats. In heart rate variability analysis, high-frequency peaks of the power spectrum densities, reflecting parasympathetic cardiovagal tone, were significantly decreased in EAM rats, but increased after left stellectomy. The ratios of phosphorylated STAT3/STAT3 (signal transducer and activator of transcription 3) and phosphorylated JAK2/JAK2 (Janus kinase 2) decreased in cell lysates of the spleen, liver, and heart in EAM rats. However, the same ratios significantly increased after left stellectomy. Nuclear factor kappaB in cell lysates of the spleen, liver, and heart increased in EAM rats, but decreased after left stellectomy. CONCLUSION: In EAM models, left stellectomy increased survival of the rats while showing antiarrhythmic effects with reduced inflammation via activation of the JAK2-STAT3-mediated signaling cascade. Our findings suggest an exciting opportunity to develop new and novel therapeutics to attenuate cardiac inflammation.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
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