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Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction.

Authors :
Li YW
Chen SX
Yang Y
Zhang ZH
Zhou WB
Huang YN
Huang ZQ
He JQ
Chen TF
Wang JF
Liu ZY
Chen YX
Source :
Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2024 Feb; Vol. 38 (1), pp. 31-41. Date of Electronic Publication: 2022 Jul 28.
Publication Year :
2024

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.<br />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 Ca <superscript>2+</superscript> concentration was assessed by a fluorometric ratio technique.<br />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 Ca <superscript>2+</superscript> influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling.<br />Conclusions: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.<br /> (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Details

Language :
English
ISSN :
1573-7241
Volume :
38
Issue :
1
Database :
MEDLINE
Journal :
Cardiovascular drugs and therapy
Publication Type :
Academic Journal
Accession number :
35900652
Full Text :
https://doi.org/10.1007/s10557-022-07326-y