FIGURE 4.

Relationship between MIRI and iron homeostasis disorder as well as ferroptosis. The pathophysiological progression of MIRI is closely associated with iron homeostasis disorder, overproduction of ROS, and mitochondrial dysfunction, followed by increased iron accumulation. These responses can further trap cardiac cells into a vicious cycle of exacerbated ROS-induced impairment, eventually leading to ferroptosis. Hearts suffering I/R injury are exposed to persistent oxidative stress, especially iron-dependent lipid hydroperoxide generation, which might damage the contractility of cardiomyocytes.