2. Academic Validation
  3. Colchicine inhibits myocardial pyroptosis and reduces myocardial cell injury after myocardial infarction through the ESR1-PI3K-Akt-NF-κB signaling pathway

Colchicine inhibits myocardial pyroptosis and reduces myocardial cell injury after myocardial infarction through the ESR1-PI3K-Akt-NF-κB signaling pathway

  • Int Immunopharmacol. 2025 May 27:156:114732. doi: 10.1016/j.intimp.2025.114732.
Yao Chen 1,  ShanQing Bao 1,  Yijie Ding 2,  GuangDong Weng 1,  ShiJie Zheng 1,  ChaoLiang Ge 3,  ChengXin Zhang 4
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
  • 2 Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China.
  • 3 The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, China.
  • 4 Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China. Electronic address: zhangchengxin@ahmu.edu.cn.
PMID: 40294468 DOI: 10.1016/j.intimp.2025.114732
Abstract

Background and purpose: Inflammation serves as a critical driver in coronary artery disease pathogenesis. Emerging clinical evidence demonstrates that low-dose colchicine therapy significantly reduces ischemic event incidence in patients with coronary heart disease while attenuating myocardial ischemia-induced inflammatory cascades. Nevertheless, the precise cardioprotective mechanisms underlying colchicine-a plant-derived anti-inflammatory agent-in limiting post-infarction cardiomyocyte injury remain incompletely elucidated. This study systematically investigates colchicine's myocardial preservation mechanisms through an integrated experimental approach.

Method: To establish experimental models of myocardial injury, we performed permanent ligation of the left anterior descending coronary artery (LAD) in mice for in vivo studies, while HL-1 mouse atrial cardiomyocytes were treated with 0.3 mM H₂O₂ to induce oxidative stress in vitro. Following successful model validation, colchicine was administered to both systems. Comprehensive evaluations included echocardiographic assessment of cardiac function, histological examination of inflammatory infiltration and Collagen deposition through H&E and Masson's trichrome staining respectively, quantitative analysis of cardiomyocyte Apoptosis by flow cytometry, and Western blot detection of key signaling pathway components and pyroptosis-related proteins (including NLRP3, Caspase-1, and GSDMD).

Result: Our experimental data revealed that colchicine treatment significantly attenuated myocardial injury and fibrosis while improving cardiac function (P < 0.05). Mechanistically, colchicine administration reduced proinflammatory cytokine release (IL-1β and IL-18), decreased neutrophil infiltration, and suppressed cardiomyocyte Pyroptosis. These cardioprotective effects were associated with modulation of the ESR1-PI3K-Akt-NF-κB signaling pathway (P < 0.05), suggesting a potential therapeutic mechanism for colchicine in myocardial protection.

Conclusion: Colchicine inhibits myocardial Pyroptosis and reduces myocardial cell injury after myocardial infarction through the ESR1-PI3K-Akt-NF-κB signaling pathway.

Keywords

Colchicine; Inflammation; Myocardial infarction; Pyroptosis.

Figures
Products