Ferroptosis: The Pivotal Link in Cardiovascular Diseases Pathogenesis and Therapy

In the pathogenesis of cardiovascular diseases (CVDs), ferroptosis is increasingly implicated as a key mechanism. This iron-driven, regulated cell death is characterized by the accumulation of lipid peroxides and a deficiency in glutathione. This comprehensive review delineates the molecular underpinnings of ferroptosis-encompassing dysregulated iron metabolism, GPX4 inactivation, and lipid peroxidation-and elucidates its pivotal role in a spectrum of cardiac pathologies. Notably, ferroptosis contributes to oxidative stress, mitochondrial dysfunction, and inflammatory responses, accelerating myocardial damage and functional decline. Emerging evidence indicates that several drugs targeting the ferroptosis pathway including iron chelators, antioxidants, and small-molecule inhibitors such as ferrostatin-1 and liproxstatin-1, demonstrate cardioprotective effects in preclinical models. However, translational challenges remain, including context-dependent roles of regulators like p53 and AMPK, and the need for organelle-specific interventions. This review synthesizes current knowledge and proposes ferroptosis as a promising target for precision medicine in CVDs, urging further research into biomarkers and combination therapies to mitigate the global burden of cardiovascular morbidity and mortality.