Molecular therapy of cardiac ischemia-reperfusion injury based on mitochondria and ferroptosis

Abstract

Excessive death of myocardial cells can lead to various cardiovascular diseases and even develop into heart failure, so developing ideal treatment plans based on pathogenesis is of great significance for cardiopathy. After the heart undergoes ischemia‒reperfusion (I/R), myocardial cells accumulate a large amount of peroxides, leading to mitochondrial dysfunction and inducing ferroptosis. Ferroptosis is a form of iron-dependent regulatory cell death (RCD) caused by imbalanced redox and iron metabolism that leads to severe cell damage through the accumulation of peroxides. The mechanism of ferroptosis is highly correlated with mitochondrial metabolism. Myocardial cells are rich in a large number of mitochondria, which serve as energy supply centers and are prone to producing reactive oxygen species (ROS), providing opportunities for oxidative stress caused by ferroptosis. Ferroptosis is related to various cardiovascular diseases, and potential treatment methods designed around ferroptosis may alter the pathological progression of cardiovascular diseases. Therefore, this review investigates the regulatory mechanisms of ferroptosis, exploring the close pathological and physiological connections between ferroptosis and mitochondrial and cardiac I/R injury. Targeting ferroptosis and mitochondria for intervention may be an effective plan for preventing and treating cardiac I/R injury.

Keywords: Cardiac ischemia–reperfusion; Ferroptosis; Mitochondria; Molecular therapy; Oxidative stress.