Effects and potential mechanisms of iron metabolism on vascular calcification

Vascular calcification (VC) is a prevalent pathological manifestation of cardiovascular and cerebrovascular diseases, and is an active, multifactor-regulated pathological process. Iron is an essential metal that maintains cellular and body functions, and its metabolic homeostasis plays a complex and crucial dual role in the development of VC. This study, based on a comprehensive analysis of numerous studies, revealed that the effect of iron on VC has a significant dose-dependent relationship: physiological concentrations or moderate amounts of iron exert protective effects by enhancing antioxidant defenses, thereby inhibiting the osteogenic phenotype transformation and apoptosis of vascular smooth muscle cells; conversely, iron overload strongly drives VC by inducing oxidative stress, ferroptosis, and pro-inflammatory responses. These findings highlight the importance of maintaining iron homeostasis. Intervention strategies targeting iron metabolism (such as iron-based phosphate binders to correct iron deficiency and iron chelators to alleviate iron overload) have potential clinical value for the prevention and treatment of VC. In summary, this review provides a novel perspective on the diagnosis and treatment of VC, and future studies need to further explore its mechanisms and conduct rigorous clinical validation to manage iron metabolism as a novel approach for personalized prevention and treatment of VC.