• Ferroptosis, an iron-dependent cell death, drives atherosclerosis by promoting endothelial ROS and lipid peroxidation.
• Intracellular iron accumulation activates pathways linked to abnormal lipid metabolism, oxidative stress, and inflammation in AS.
• GPX4 and system Xc- are central protective mechanisms against ferroptosis, offering therapeutic targets for AS.
• Targeting ferroptosis presents a novel strategy to inhibit atherosclerotic progression and stabilize plaques.