Verapamil attenuates myocardial ischemia/reperfusion injury by inhibiting apoptosis via activating the JAK2/STAT3 signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 180; p. 117568
• Main Authors: Zhao, Yang, Huang, Weiyi, Liu, Fang, Sun, Qiang, Shen, Daifei, Fan, Wenjun, Huang, Danmei, Zhang, Yanmei, Gao, Fenfei, Wang, Bin
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-11-2024; Elsevier
• Subjects: Apoptosis; Hypoxia/reoxygenation; JAK2/STAT3 signaling pathway; Myocardial ischemia/reperfusion injury; Verapamil; Verapamil; Myocardial ischemia/reperfusion injury; Hypoxia/reoxygenation; JAK2/STAT3 signaling pathway; Apoptosis
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117568

Apoptosis is a crucial pathological process in myocardial ischemia/reperfusion injury (MIRI). Verapamil (Ver), normally used to treat hypertension or heart rhythm disorders, also attenuates MIRI. The potential of Ver to inhibit apoptosis and thereby attenuate MIRI remains unclear, as does the mechanism. We established an in vivo mouse ischemia/reperfusion (I/R) model by occlusion of the left anterior descending coronary. To construct a hypoxia/reoxygenation model in vitro, H9c2 cardiomyocytes were immersed in a hypoxic buffer in a hypoxia/anaerobic workstation. Ver significantly improved cardiac function and reduced myocardial infarction size in I/R mice, while decreasing apoptosis. Both in vivo and in vitro, application of Ver activated the JAK2/STAT3 signaling pathway and elevated Bcl-2 expression, while decreasing Bax and cleaved caspase-3 levels. Treatment with AG490, a JAK2 inhibitor, partially counteracted the anti-apoptotic and the cardioprotective effect of Ver. Thus, we conclude that Ver alleviates MIRI by reducing apoptosis via the JAK2/STAT3 signaling pathway activation. These findings provide a novel mechanism of Ver in the treatment of MIRI.
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•Verapamil attenuates cellular apoptosis induced by hypoxia/reoxygenation or myocardial ischemia/reperfusion.•Verapamil enhances the activation of the JAK2/STAT3 signaling pathway in myocardial ischemia/reperfusion injury.•The therapeutic effect of verapamil on myocardial I/R injury is abrogated by JAK2 inhibitors.