Types, Molecular Mechanisms, and Potential Therapeutic Targets of Programmed Endothelial Cell Death in Atherosclerosis

ABSTRACT: Atherosclerosis is a chronic progressive disease that occurs in the inner walls of arteries. Endothelial dysfunction is a key component in the early stages of atherosclerosis. Unhealthy lifestyle factors (eg, smoking), hypertension, hyperglycemia, and hyperlipidemia are important risk factors that may induce endothelial cell injury or even lead to cellular death. Hypertension contributes to atherosclerosis by exerting mechanical stress that damages endothelial cells. Current studies have shown that vascular endothelial cells are mainly involved in programmed cell death pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, cuproptosis, parthanatos, and NETosis. This review synthesizes current knowledge on programmed cell death pathways in vascular endothelia during atherogenesis, delineating their triggering factors, molecular underpinnings, and potential regulatory targets.