Ferritinophagy in cardiovascular diseases: mechanisms and potential therapy

Abstract

The process of ferritinophagy, which involves the selective autophagic breakdown of ferritin triggered by nuclear receptor coactivator 4 (NCOA4), has been shown to regulate ferroptosis. Recent studies have confirmed that ferritinophagy plays a key role in the formation and progression of cardiovascular diseases. The mechanism of ferritinophagy involves the phagocytosis of ferritin by NCOA4, which binds ferritin and delivers it to the autophagosome. There, it fuses with lysosomes to degrade ferritin and release iron. This process is not only involved in iron-dependent responses, but also in the progression of a variety of human diseases, including metabolism-related diseases, neurodegenerative diseases, cardiovascular diseases, and infectious diseases. In cardiovascular diseases, ferritinophagy plays a central role in inducing ferroptosis, a mode of programmed cell death caused by lipid peroxidation. This process is regulated by intracellular iron homeostasis and reactive oxygen species production. It has been demonstrated that ferritinophagy promotes ferroptosis by increasing intracellular iron content. Furthermore, the influence of ferritinophagy in cardiovascular diseases has been further demonstrated. For instance, ischemia-reperfusion injury, atherosclerosis, myocardial disease and heart failure are all associated with ferritin levels. The early detection of ferritin levels, maintenance of iron homeostasis, prevention of iron overload and exploration of the interrelationship between ferritinophagy and cardiac diseases can provide new ideas for the prevention and treatment of cardiovascular diseases. Therapeutic options for ferritinophagy are also being explored. For instance, the inhibition of O-GlcNAcylation modification has been shown to promote ferritinophagy, which releases iron stored in ferritin and further regulates ferroptosis. Ferritinophagy has been demonstrated to play an important role in the formation and progression of cardiovascular diseases, influencing disease development by regulating iron homeostasis and ferroptosis. Future studies may further reveal the specific mechanisms and develop new therapeutic strategies.

Keywords: Cardiovascular disease; Ferritinophagy; NCOA4.