The Role of Glutathione Peroxidase 4 in Atherosclerosis: Role and Therapeutic Potential.

Atherosclerosis, characterized by abnormal lipid metabolism and inflammation, constitutes the fundamental pathological basis for the development of cardiovascular lesions. Ferroptosis, a recently discovered novel form of cell death, is linked to disturbances in iron metabolism and lipid peroxidation; meanwhile, an association with various cardiovascular diseases, including heart failure, myocardial infarction, and atherosclerosis, has also been confirmed. Glutathione peroxidase 4 (GPX4) is an important component of the antioxidant system that plays a key role in maintaining iron homeostasis and inhibiting ferroptosis. Ferroptosis triggered by GPX4 inactivation can also further activate pyroptosis pathways by releasing proinflammatory signals, thereby collectively exacerbating inflammation and the progression of atherosclerotic plaques. Therefore, further investigations into the function of GPX4 in atherosclerosis may facilitate the development of novel diagnostic and therapeutic approaches, as well as drug development targets for the prevention and prognosis of related cardiovascular diseases. Moreover, the activation of GPX4 or the supplementation with its coenzyme, glutathione (GSH), may emerge as a promising new therapeutic strategy. This review summarizes the structure and function of GPX4 and the role of this enzyme in iron toxicity and atherosclerosis.