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Celastrol exerts antiarrhythmic effects in chronic heart failure via NLRP3/Caspase-1/IL-1β signaling pathway

Wuping Tan1, Siyi Cheng1, Qinfang Qiu1

  • 1Cardiovascular 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 Autonomic Nervous System Modulation, PR China; Institute of Molecular Medicine, Renmin Hospital of Wuhan University, PR China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, PR China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 13, 2024
PubMed

Insights

Celastrol significantly reduces ventricular arrhythmias after myocardial infarction by improving heart rate variability and inhibiting inflammation. This study reveals celastrol

Area of Science:

  • Cardiology
  • Pharmacology
  • Cell Biology

Background:

  • Celastrol exhibits therapeutic potential, including cardioprotective effects.
  • Ventricular arrhythmias (VAs) post-myocardial infarction (MI) remain a clinical challenge.
  • Celastrol's role in mitigating VAs after MI requires further investigation.

Purpose of the Study:

  • To investigate the mechanisms by which celastrol regulates VAs and cardiac electrophysiology in a rat model of MI.
  • To explore celastrol's effects on autonomic nerve and ion channel remodeling.
  • To assess celastrol's impact on myocardial fibrosis and inflammation.

Main Methods:

  • Establishment of MI model in Sprague-Dawley rats with sham, MI, and MI + celastrol groups.
  • Assessment of electrocardiogram, heart rate variability (HRV), and ventricular electrophysiology.
  • Histological analysis, ELISA, Western blotting, and qRT-PCR to elucidate molecular mechanisms.
  • In vitro study using H9c2 cells under hypoxic conditions and NLRP3 inflammasome activation.

Main Results:

  • Celastrol significantly alleviated cardiac electrophysiological instability and improved HRV in MI rats.
  • Upregulation of Cx43, Kv4.2, Kv4.3, and Cav1.2 ion channels observed with celastrol treatment.
  • Celastrol mitigated myocardial fibrosis and inhibited the NLRP3 inflammasome pathway.
  • In vitro experiments confirmed celastrol's regulatory effects on the NLRP3 inflammasome.

Conclusions:

  • Celastrol alleviates VAs post-MI by promoting autonomic nerve and ventricular electrical remodeling.
  • Celastrol facilitates ion channel remodeling and reduces ventricular fibrosis and inflammation.
  • The protective effects are partly mediated through inhibition of the NLRP3/Caspase-1/IL-1β pathway.
Abstract

Keywords:
Autonomic nerve remodelingCelastrolMyocardial infarctionVentricular arrhythmiasVentricular electrical remodeling

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