ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update

Abstract

The cardiomyocyte is an essential component of the heart, communicating and coordinating with non-cardiomyocytes (endothelial cells, fibroblasts, and immune cells), and are critical for the regulation of structural deformation, electrical conduction, and contractile properties of healthy and remodeled myocardium. Reactive oxygen species (ROS) in cardiomyocytes are mainly produced by the mitochondrial oxidative respiratory chain, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), xanthine oxidoreductase (XOR), monoamine oxidase (MAO), and p66shc. Under physiological conditions, ROS are involved in the regulation of cardiac development and cardiomyocyte maturation, cardiac calcium handling, and excitation-contraction coupling. In contrast, dysregulation of ROS metabolism is involved in the development and progression of cardiovascular diseases (CVDs), including myocardial hypertrophy, hyperlipidemia, myocardial ischemia/reperfusion injury, arrhythmias and diabetic cardiomyopathy. Further oxidative stress induced by ROS dyshomeostasis was found to be the major reason for cardiomyocyte death in cardiac diseases, and in recent years, ferroptosis induced by oxidative stress have been considered to be fatal to cardiomyocytes. In addition, ROS is also a key trigger for the activation of pyroptosis, which induces and exacerbates the inflammatory response caused by various cardiac diseases and plays a critical role in CVDs. Therefore, in this review, the sources and destinations of ROS in cardiomyocytes will be systematically addressed, so as to reveal the molecular mechanisms by which ROS accumulation triggers cardiomyocyte ferroptosis and pyroptosis under pathological conditions, and provide a new concept for the research and treatment of heart-related diseases.