Regulated cell death in myocardial ischemia–reperfusion injury

• Published in: Trends in endocrinology and metabolism Vol. 35; no. 3; pp. 219 - 234
• Main Authors: Xiang, Qi, Yi, Xin, Zhu, Xue-Hai, Wei, Xiang, Jiang, Ding-Sheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2024
• Subjects: ferroptosis; inflammation; myocardial ischemia–reperfusion injury; necroptosis; pyroptosis; pyroptosis; myocardial ischemia–reperfusion injury; ferroptosis; inflammation; necroptosis
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2023.10.010

The death of cardiomyocytes is the basic pathological factor inducing irreversible injury during myocardial ischemia/reperfusion, including increasing infarct size, cardiac remodeling, and heart failure.Despite debates about their precise mechanisms inducing myocardial ischemia/reperfusion (I/R) injury, ferroptosis, necroptosis, and pyroptosis all contribute to the pathological process of myocardial I/R injury.Ferroptosis and necroptosis both occur in the late reperfusion phase and persist for a long time, even though ferroptotic signals appear during ischemia. Pyroptosis, by contrast, takes place in the early reperfusion phase and is tightly related to chronic inflammation via the NLRP3 inflammasome.There is extensive crosstalk between ferroptosis, necroptosis, and pyroptosis, and accumulating evidence indicates an advantage of their combined inhibition to attenuate myocardial I/R injury. Myocardial ischemia–reperfusion (I/R) injury most commonly occurs in coronary artery disease when prompt reperfusion is used to salvage the ischemic myocardium. Cardiomyocyte death is a significant component of myocardial I/R injury and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of cell death, ferroptosis, necroptosis, and pyroptosis have been shown to be involved in myocardial I/R. These new forms of regulated cell death cause cardiomyocyte loss and exacerbate I/R injury by affecting reactive oxygen species (ROS) generation, calcium stress, and inflammatory cascades, subsequently mediating adverse remodeling, cardiac dysfunction, and heart failure. Herein, we review the roles of ferroptosis, necroptosis, and pyroptosis in myocardial I/R and discuss their contribution to pathology. Myocardial ischemia–reperfusion (I/R) injury most commonly occurs in coronary artery disease when prompt reperfusion is used to salvage the ischemic myocardium. Cardiomyocyte death is a significant component of myocardial I/R injury and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of cell death, ferroptosis, necroptosis, and pyroptosis have been shown to be involved in myocardial I/R. These new forms of regulated cell death cause cardiomyocyte loss and exacerbate I/R injury by affecting reactive oxygen species (ROS) generation, calcium stress, and inflammatory cascades, subsequently mediating adverse remodeling, cardiac dysfunction, and heart failure. Herein, we review the roles of ferroptosis, necroptosis, and pyroptosis in myocardial I/R and discuss their contribution to pathology.