Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Oct;18(5):1042-1057.
doi: 10.1007/s12265-025-10661-8. Epub 2025 Jul 21.

Copper Homeostasis and Cuproptosis As Potential Intervention Strategy in Atherosclerosis

Jingchun Xie #  1 , Liuyan Xin #  2 , Qi Jin  1 , An Li  2 , Jinping Li  3 , Baoping Xie  4
Affiliations
Review

Copper Homeostasis and Cuproptosis As Potential Intervention Strategy in Atherosclerosis

Jingchun Xie et al. J Cardiovasc Transl Res. 2025 Oct.

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.

Keywords: Atherosclerosis; Copper; Cuproptosis; Endogenous metabolites.

PubMed Disclaimer

Conflict of interest statement

Declarations: This is an original review and all data and materials in the manuscript have not been published in other journals or media. Ethics Approvale: Not applicable. Patient Consent for Publication: Not applicable. Competing Interests: All authors have declared that there are no competing interests.

References

    1. Libby P. The changing landscape of atherosclerosis. Nature. 2021;592:524–33. https://doi.org/10.1038/s41586-021-03392-8 . - DOI - PubMed
    1. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25. https://doi.org/10.1038/nature10146 . - DOI - PubMed
    1. Su W, Zhao Y, Wei Y, Zhang X, Ji J, Yang S. Exploring the pathogenesis of psoriasis complicated with atherosclerosis via microarray data analysis. Front Immunol. 2021;12:667690. https://doi.org/10.3389/fimmu.2021.667690 . - DOI - PubMed - PMC
    1. De Meyer G, Zurek M, Puylaert P, Martinet W. Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets. Nat Rev Cardiol. 2024;21:312–25. https://doi.org/10.1038/s41569-023-00957-0 . - DOI - PubMed
    1. Tawakol A, Abohashem S, Zureigat H. Imaging apoptosis in atherosclerosis: from cell death, a ray of light. J Am Coll Cardiol. 2020;76:1875–7. https://doi.org/10.1016/j.jacc.2020.09.010 . - DOI - PubMed

LinkOut - more resources