Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases

Yang Yang; Qi Feng; Ying Luan; Hui Liu; Yuxue Jiao; Huijie Hao; Bo Yu; Yi Luan; Kaidi Ren

doi:10.3389/fphar.2023.1229297

Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases

Front Pharmacol. 2023 Aug 11:14:1229297. doi: 10.3389/fphar.2023.1229297. eCollection 2023.

Authors

Yang Yang¹, Qi Feng^{2

3}, Ying Luan⁴, Hui Liu⁵, Yuxue Jiao¹, Huijie Hao⁶, Bo Yu⁶, Yi Luan¹, Kaidi Ren^{7

8}

Affiliations

¹ Clinical Systems Biology Research Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Research Institute of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
⁵ School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
⁶ Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
⁷ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁸ Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.

Abstract

Copper (Cu) is a vital trace element for maintaining human health. Current evidence suggests that genes responsible for regulating copper influx and detoxification help preserve its homeostasis. Adequate Cu levels sustain normal cardiac and blood vessel activity by maintaining mitochondrial function. Cuproptosis, unlike other forms of cell death, is characterized by alterations in mitochondrial enzymes. Therapeutics targeting cuproptosis in cardiovascular diseases (CVDs) mainly include copper chelators, inhibitors of copper chaperone proteins, and copper ionophores. In this review, we expound on the primary mechanisms, critical proteins, and signaling pathways involved in cuproptosis, along with its impact on CVDs and the role it plays in different types of cells. Additionally, we explored the influence of key regulatory proteins and signaling pathways associated with cuproptosis on CVDs and determined whether intervening in copper metabolism and cuproptosis can enhance the outcomes of CVDs. The insights from this review provide a fresh perspective on the pathogenesis of CVDs and new targets for intervention in these diseases.

Keywords: cardiomyocytes; cardiovascular disease (CVD); copper (Cu); cuproptosis; intervention targets.

Publication types

Review

Grants and funding

This work was supported by the National Natural Science Foundation of China (Nos. 82204389 and 31900502), the Henan Medical Science and Technology Joint Building Program (Nos. LHGJ20190236, LHGJ20190227, and LHGJ20200310), the Medical Science and Technology Research Project of Henan Province (SBGJ202103079), the Natural Science Foundation of Henan (222300420284), the Tianjin Municipal Science and Technology Commission (21JCQNJC01630), the National Natural Science Young Scientists Foundation of China (82200796), the China Postdoctoral Science Foundation (2022M722901), and the Medical Science and Technology Research Project of Henan Province (SBGJ202102145).