Role of ferroptosis in vascular calcification diseases

Ferroptosis, as an iron-dependent form of cell death, plays a crucial role in the onset and progression of vascular calcification (VC). Its core mechanisms involve intracellular iron overload, accumulation of lipid per oxidation, and the failure of antioxidant systems represented by GPX4/GSH. In the context of chronic kidney disease, diabetes, and atherosclerosis, processes of ferroptosis, such as the inhibition of the SLC7A11-GPX4 pathway, lipid metabolism disorders, and ferritinophagy, promote the osteoblast-like trans-differentiation of vascular smooth muscle cells (VSMCs); enhance oxidative stress and inflammatory responses, thereby accelerating calcium and phosphate deposition and vascular calcification. Targeting ferroptosis pathways significantly reduces calcification in experimental models, suggesting potential therapeutic strategies for VC.