2. Academic Validation
  3. Colchicine prevents atrial fibrillation promotion by inhibiting IL-1β-induced IL-6 release and atrial fibrosis in the rat sterile pericarditis model

Colchicine prevents atrial fibrillation promotion by inhibiting IL-1β-induced IL-6 release and atrial fibrosis in the rat sterile pericarditis model

  • Biomed Pharmacother. 2020 Sep;129:110384. doi: 10.1016/j.biopha.2020.110384.
Qiongfeng Wu 1,  Huixia Liu 2,  Jie Liao 1,  Ning Zhao 1,  Gary Tse 3,  Bin Han 4,  Lei Chen 5,  Zhengrong Huang 6,  Yimei Du 7
Affiliations

Affiliations

  • 1 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China; Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China; Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.
  • 4 Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
  • 5 Department of Physiology, Nanjing Medical University, Nanjing, China.
  • 6 Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address: huangzhengrong@xmu.edu.cn.
  • 7 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yimeidu@mail.hust.edu.cn.
PMID: 32554248 DOI: 10.1016/j.biopha.2020.110384
Abstract

A few clinical trials have recently reported the potential effect of colchicine in preventing post-operative atrial fibrillation (POAF) and early atrial fibrillation (AF) recurrence after catheter pulmonary vein isolation. However, the molecular mechanisms through which colchicine inhibits AF remain unclear. We aim to assess the anti-AF effect of colchicine in the rat sterile pericarditis (SP) model and to investigate its molecular mechanisms. SP was induced in Sprague-Dawley rats by the epicardial application of sterile talc. Treatment with colchicine or vehicle began 1 d before pericardiotomy. AF was induced by transesophageal burst pacing on day 3 after surgery. Treatment with colchicine reduced the duration of AF and the probability of induction of AF in SP rats. The dose of 0.5 mg kg-1·day-1 had the best effect. Such treatment also reduced neutrophil infiltration, the mRNA expression of IL-6, TGF-β, and TNF-α, atrial fibrosis, fibrosis related genes, and signal molecules (STAT3, P38, and Akt). Meanwhile, the release of IL-1β (4-24 h) and IL-6 (4-72 h) in atria after surgery was significantly inhibited by colchicine. In cultured rat cardiac fibroblasts, colchicine treatment inhibited IL-1β-induced expression of IL-6, which was accompanied by significantly decreased phosphorylation of P38, Akt, JNK, and NFκB. Interestingly, the supplementation of IL-6 abolished the anti-AF effect of colchicine in SP rats. Colchicine prevents AF in SP rats through the inhibition of IL-1β-induced IL-6 release and subsequent atrial fibrosis. However, further studies are required to investigate whether colchicine inhibits POAF through other mechanisms.

Keywords

Atrial fibrillation; Atrial fibrosis; Colchicine; IL-1β; IL-6.

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