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Celastrol exerts antiarrhythmic effects in chronic heart failure via NLRP3/Caspase-1/IL-1ß signaling pathway.
Tan, Wuping; Cheng, Siyi; Qiu, Qinfang; Huang, Jiaxing; Xie, Mengjie; Song, Lingpeng; Zhou, Zhen; Wang, Yijun; Guo, Fuding; Jin, Xiaoxing; Li, Zeyan; Xu, Xiao; Jiang, Hong; Zhou, Xiaoya.
Afiliação
  • Tan W; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Cheng S; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Qiu Q; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Huang J; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Xie M; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Song L; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Zhou Z; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Wang Y; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Guo F; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Jin X; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Li Z; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Xu X; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Jiang H; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
  • Zhou X; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, PR China; Cardiac Autonomic Nervous System Research Center of Wuhan University, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, PR China; Hubei Key Laboratory of
Biomed Pharmacother ; 177: 117121, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39002443
ABSTRACT

OBJECTIVES:

Celastrol has widespread therapeutic applications in various pathological conditions, including chronic inflammation. Previous studies have demonstrated the potent cardioprotective effects of celastrol. Nevertheless, limited attention has been given to its potential in reducing ventricular arrhythmias (VAs) following myocardial infarction (MI). Hence, this study aimed to elucidate the potential mechanisms underlying the regulatory effects of celastrol on VAs and cardiac electrophysiological parameters in rats after MI.

METHODS:

Sprague-Dawley rats were divided at random the sham, MI, and MI + celastrol groups. The left coronary artery was occluded in the MI and MI + Cel groups. Electrocardiogram, heart rate variability (HRV), ventricular electrophysiological parameters analysis, histology staining of ventricles, Enzyme-linked immunosorbent assay (ELISA), western blotting and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to elucidate the underlying mechanism of celastrol. Besides, H9c2 cells were subjected to hypoxic conditions to create an in vitro model of MI and then treated with celastrol for 24 hours. Nigericin was used to activate the NLRP3 inflammasome.

RESULTS:

Compared with that MI group, cardiac electrophysiology instability was significantly alleviated in the MI + celastrol group. Additionally, celastrol improved HRV, upregulated the levels of Cx43, Kv.4.2, Kv4.3 and Cav1.2, mitigated myocardial fibrosis, and inhibited the NLRP3 inflammasome pathway. In vitro conditions also supported the regulatory effects of celastrol on the NLRP3 inflammasome pathway.

CONCLUSIONS:

Celastrol could alleviate the adverse effects of VAs after MI partially by promoting autonomic nerve remodeling, ventricular electrical reconstruction and ion channel remodeling, and alleviating ventricular fibrosis and inflammatory responses partly by through inhibiting the NLRP3/Caspase-1/IL-1ß pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Transdução de Sinais / Ratos Sprague-Dawley / Caspase 1 / Interleucina-1beta / Triterpenos Pentacíclicos / Proteína 3 que Contém Domínio de Pirina da Família NLR / Insuficiência Cardíaca / Antiarrítmicos / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article País de publicação: França
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Transdução de Sinais / Ratos Sprague-Dawley / Caspase 1 / Interleucina-1beta / Triterpenos Pentacíclicos / Proteína 3 que Contém Domínio de Pirina da Família NLR / Insuficiência Cardíaca / Antiarrítmicos / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article País de publicação: França