Gemfibrozil mitigates caspase-11-driven myocardial pyroptosis in ischemia/reperfusion injury in mice
The size of the infarct area following acute myocardial infarction (AMI) is a critical prognostic factor. Caspase-11-dependent pyroptosis has been implicated as a key mechanism driving cardiomyocyte death after AMI. However, no therapeutic agents have been developed to inhibit myocardial cell death...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Journal of Molecular and Cellular Cardiology Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S277297612500011X |
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| Summary: | The size of the infarct area following acute myocardial infarction (AMI) is a critical prognostic factor. Caspase-11-dependent pyroptosis has been implicated as a key mechanism driving cardiomyocyte death after AMI. However, no therapeutic agents have been developed to inhibit myocardial cell death by targeting caspase-11. This study investigates the effects of gemfibrozil, a potential caspase-11 inhibitor, on ischemia/reperfusion-induced myocardial pyroptosis in mice. To model AMI, the left coronary artery of C57BL/6 N mice was ligated for 1 h, followed by reperfusion. Levels of cleaved caspase-11 and the N-terminal fragment of gasdermin D (GSDMD-N) in ischemic myocardial tissue increased progressively over time after ischemia/reperfusion. Gemfibrozil treatment during reperfusion significantly attenuated these increases in cleaved caspase-11 and GSDMD-N levels. Moreover, gemfibrozil reduced the extent of myocardial infarct size during reperfusion. In cultured cardiomyocytes isolated from adult mice, hypoxia/reoxygenation-induced increases in caspase-11 and GSDMD cleavage were similarly mitigated by gemfibrozil, which concurrently prevented necrotic cell death. These findings demonstrate the involvement of caspase-11-dependent pyroptosis in myocardial cell death following ischemia/reperfusion and suggest that gemfibrozil holds promise as a therapeutic agent for reducing myocardial infarct size after AMI. |
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| ISSN: | 2772-9761 |