Ferroptosis of Macrophages and Endothelial Cells in Atherosclerosis: Molecular Mechanisms and Therapeutic Targets

Atherosclerosis (AS) is a significant contributor to cardiovascular disease, characterized by abnormal lipid metabolism, cellular apoptosis, oxidative stress, and chronic inflammation. Ferroptosis represents a form of non-apoptotic programmed cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS) and the peroxidation of membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). The ferroptosis of endothelial cells (ECs) and macrophages plays a crucial role in the development of atherosclerotic plaques. This review summarizes the mechanisms and associated therapeutic targets related to ferroptosis in macrophages and ECs within the context of AS. Recent research has made substantial progress in elucidating the mechanisms through which ferroptosis influences AS progression; however, a comprehensive understanding of the precise molecular basis for AS remains essential. Moreover, further clinical trials of drugs targeting ferroptosis are necessary. This review updates the knowledge of ferroptosis in ECs and macrophages related to AS, identifies potential links and the subsequent implications for plaque stability, and serves as a reference for developing new pharmacological strategies to address AS and stabilize vulnerable plaques.