铜死亡与动脉粥样硬化的关系及其靶向治疗的研究进展OA北大核心

Atherosclerosis(AS),a chronic and multifactorial vascular disease,involves diverse pathological processes including dyslipidemia,reactive oxygen species(ROS)generation,inflammatory cell infiltration,and local thrombosis.In recent years,cuproptosis,a novel form of copper-dependent programmed cell death,has attracted considerable attention.It is primarily triggered by the binding of excessive copper ions to lipoylated proteins,resulting in disruption of the tricarboxylic acid(TCA)cycle,damage to iron-sulfur cluster proteins,and consequent functional impairment of related enzymes and proteins,ultimately inducing cell death through multiple pathways.Previous studies have revealed the close association between cuproptosis and AS pathogenesis.Cuproptosis promotes ROS production,induces lipid peroxidation via the Fenton reaction,triggers inflammatory responses and disrupts mitochondrial TCA cycle,thereby compromising the functions of vascular cells(macrophages,endothelial cells,and smooth muscle cells),destabilizing plaques and exacerbating AS progression.Therefore,targeting cuproptosis may present a new direction for AS treatment and its complication prevention.Specifically,cuproptosis-related genes may serve as potential diagnostic biomarkers for AS,and pharmacological inhibition of cuproptosis has been shown to significantly modulate disease progression,highlighting the potential value of targeting cuproptosis in AS management.This review systematically summarizes the molecular mechanisms of copper metabolism and cuproptosis,their pathophysiological roles in AS,and recent advances in targeting cuproptosis for AS diagnosis and treatment,aiming to provide novel insights into clinical strategies for AS prevention and therapy.