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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 1/2024

28-07-2022 | Colchicine | Original Article

Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction

Authors: Yue-wei Li, Si-xu Chen, Ying Yang, Zeng-hui Zhang, Wei-bin Zhou, Yu-na Huang, Zhao-qi Huang, Jia-qi He, Ting-feng Chen, Jing-feng Wang, Zhao-yu Liu, Yang-xin Chen

Published in: Cardiovascular Drugs and Therapy | Issue 1/2024

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Abstract

Purpose

Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs.

Methods

Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2′,7′-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique.

Results

We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling.

Conclusions

Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.
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Metadata
Title
Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction
Authors
Yue-wei Li
Si-xu Chen
Ying Yang
Zeng-hui Zhang
Wei-bin Zhou
Yu-na Huang
Zhao-qi Huang
Jia-qi He
Ting-feng Chen
Jing-feng Wang
Zhao-yu Liu
Yang-xin Chen
Publication date
28-07-2022
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 1/2024
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-022-07326-y

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