Abstract:Ferritinophagy is a selective autophagic process mediated by nuclear receptor coactivator 4 (NCOA4), which directs the degradation of the iron-storage protein ferritin to release bioavailable iron, thereby playing a pivotal role in the regulation of ferroptosis. Ferroptosis is a distinct form of programmed cell death characterized by its dependency on iron and driven by lipid peroxidation, and it has garnered growing attention in recent years within the field of cell death research. In the cardiovascular system, the coordinated regulation of ferritinophagy and ferroptosis is essential for maintaining iron homeostasis and cellular metabolic balance. However, dysregulation or sustained activation of this pathway may result in iron overload, oxidative stress, and lipid peroxidation, ultimately contributing to myocardial injury, atherosclerosis, and heart failure, thereby accelerating disease progression. Recent studies have highlighted the significant therapeutic potential of targeting the ferritinophagy/ferroptosis axis using iron chelators, antioxidants, and ferroptosis inhibitors in the treatment of cardiovascular diseases. This review provides a comprehensive overview of the molecular mechanisms underlying ferritinophagy and ferroptosis, elucidates their roles and crosstalk in the onset and progression of cardiovascular disorders, and critically evaluates emerging targeted therapeutic strategies. The aim is to offer a theoretical foundation and novel clinical insights for the precision management of cardiovascular diseases.
