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铜稳态与铜死亡作为动脉粥样硬化潜在干预策略

Copper Homeostasis and Cuproptosis As Potential Intervention Strategy in Atherosclerosis.

作者信息

Xie Jingchun, Xin Liuyan, Jin Qi, Li An, Li Jinping, Xie Baoping

机构信息

Yudu Hospital Affiliated to Gannan Medical University, Ganzhou, Jiangxi, 341000, People's Republic of China.

First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, People's Republic of China.

出版信息

J Cardiovasc Transl Res. 2025 Jul 21. doi: 10.1007/s12265-025-10661-8.

Abstract

Atherosclerosis (AS) is a vascular disorder characterized by lipid accumulation, fibrous tissue proliferation, and calcium deposition in the intima, contributing significantly to the mortality associated with cardiovascular disease, and the pathogenesis of AS is multifaceted. Recent studies have identified copper (Cu) overlap induced cuproptosis as a key mechanism underlying cellular dysfunction in AS. Cuproptosis impacts the function and survival of multiple cell types within AS lesions by several downstream pathways, and regulating cellular cuproptosis may be a very promising clinical treatment strategy. In this review, we explored the influence of key regulatory proteins and signaling pathways associated with copper homeostasis and cuproptosis in AS, and the potential regulators of cuproptosis in AS therapy, especially the endogenous metabolites, copper ionophore, Cu oxide nanoparticles and natural products, we also discuss emerging therapeutic strategies and offering insights into future developments and translational medicine or challenge by targeting cuproptosis in AS pathogenesis.

摘要

动脉粥样硬化(AS)是一种血管疾病,其特征在于脂质蓄积、纤维组织增生以及内膜中的钙沉积,这对心血管疾病相关的死亡率有显著影响,并且AS的发病机制是多方面的。最近的研究已确定铜(Cu)重叠诱导的铜死亡是AS中细胞功能障碍的关键机制。铜死亡通过几种下游途径影响AS病变内多种细胞类型的功能和存活,并且调节细胞铜死亡可能是一种非常有前景的临床治疗策略。在本综述中,我们探讨了与AS中铜稳态和铜死亡相关的关键调节蛋白和信号通路的影响,以及AS治疗中铜死亡的潜在调节因子,特别是内源性代谢物、铜离子载体、氧化铜纳米颗粒和天然产物,我们还讨论了新兴的治疗策略,并针对AS发病机制中靶向铜死亡提供了对未来发展以及转化医学或挑战的见解。

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