NOX4 and heart failure: Knocking down FTH in cardiomyocytes prevents free iron from being stored in ferritin, increases unstable iron pools, promotes intracellular ROS production, activates oxidative stress, and causes ferroptosis in cardiomyocytes, leading to age-related heart damage.472 A high-iron diet significantly reduces SLC7A11 expression and GSH levels, and exacerbating cardiac injury and myocardial hypertrophy in cardiomyocyte-specific FTH knockout mice.67 Additionally, the Toll-like receptor 4 (TLR4)/NADPH oxidase 4 (NOX4) pathway plays a role in heart failure associated with ferroptosis.