Colchicine prevents ventricular arrhythmias vulnerability in diet-induced obesity rats

Biochem Biophys Res Commun. 2022 Jun 25:610:127-132. doi: 10.1016/j.bbrc.2022.03.114. Epub 2022 Apr 16.

Abstract

Aims: This study aimed to assess the role of colchicine in ventricular arrhythmias (VAs) induced by high fat diet (HFD)-fed rats.

Methods and results: Male rats were divided into four groups: CTL, normal diet plus saline; CTC, normal diet plus colchicine; HFD, HFD plus saline; HFC: HFD plus colchicine. Metabolic parameters, ECG parameters, ventricular electrophysiological parameters, ventricular histology, Western blot and RT-qPCR were measured. Compared with the HFD group, colchicine treatment significantly improved metabolic parameters, reduced ventricular fibrosis, increased the expression of Cav1.2, Kv4.2, Nav1.5, and Cx43, reduced CaMKII, p-CaMKII, p-RyR2 (S2808), and p-RyR2 (S2814) expression in LV. Furthermore, colchicine inhibited the inflammatory responses, prolonged ventricular effective refractory period (ERP), reduced corrected QT interval (QTc) and Tpeak-Tend interval, so as to reduce the susceptibility to VAs in obesity rats.

Conclusions: Colchicine could mitigate ventricular fibrosis, ventricular electrical remodeling, as well as the expression of ion channels, and inhibit obesity-induced inflammatory responses, which provides a new idea for colchicine to prevent VAs in obese individuals.

Keywords: Colchicine; High fat diet; Inflammation; Ventricular arrhythmia.

MeSH terms

  • Animals
  • Arrhythmias, Cardiac* / drug therapy
  • Arrhythmias, Cardiac* / etiology
  • Arrhythmias, Cardiac* / prevention & control
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Colchicine* / pharmacology
  • Diet, High-Fat / adverse effects
  • Fibrosis
  • Male
  • Obesity* / complications
  • Obesity* / etiology
  • Rats
  • Ryanodine Receptor Calcium Release Channel
  • Ventricular Remodeling

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Colchicine