Articles
Vol. 70 No. 4 (2026)
https://doi.org/10.4081/ejh.2026.4586

Dopamine beta-hydroxylase mediates atherosclerosis progression by regulating copper metabolism via PHOX2A

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Published: 27 October 2026
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Atherosclerosis, dopamine β-hydroxylase, PHOX2A, copper metabolism, cuproptosis

Authors

Qingquan Xue
Department of Vascular Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, China.
Guilin Feng
Department of Vascular Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, China.
Jiqiong Hu
Department of Vascular Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, China.
Fangkuan Li
Department of Vascular Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, China.
Shusen Tang
kkxxhsw@126.com
Department of Electrical Science, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, China.

Atherosclerosis (AS) is a major cardiovascular disease whose underlying molecular mechanisms remain incompletely understood. This study investigates the role of dopamine beta-hydroxylase (DBH) in AS pathogenesis and its regulation of copper metabolism via the transcription factor PHOX2A. Through transcriptomic profiling of aortic tissues from ApoE⁻/⁻ mice fed a high-fat diet, we identified 2891 differentially expressed genes (DEGs) between AS and control mice, with DBH being significantly upregulated. DBH expression was also elevated in the serum of AS patients and in ox-LDL-treated human vascular smooth muscle cells (HVSMCs). Mechanistically, we demonstrate that PHOX2A directly activates the DBH promoter, and that DBH knockdown attenuates ox‑LDL‑induced apoptosis and lipid accumulation in HVSMCs while PHOX2A overexpression exacerbates these effects. Importantly, DBH knockdown in ApoE⁻/⁻ mice not only reduced atherosclerotic plaque burden and improved serum lipid profiles but also restored serum copper concentrations and altered the expression of cuproptosis‑related proteins (FDX1, LIAS, DLAT). These findings identify DBH as a key mediator of AS progression linked to PHOX2A‑dependent regulation of copper metabolism and cuproptosis, suggesting that targeting the DBH/PHOX2A axis may represent a novel therapeutic strategy for AS.

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Ethics Approval

The ethical approval for this study was granted by the Ethics Committee of The First Affiliated Hospital of Wannan Medical University; written informed consent was obtained from all participants prior to their inclusion in the study., All animal experiments were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Wannan Medical College.

CRediT authorship contribution

Qingquan Xue, conceptualization, methodology, formal analysis, investigation, writing – original draft, writing – review & editing. Guilin Feng, formal analysis. Jiqiong Hu, formal analysis. Fangkuan Li, formal analysis, writing – review & editing. Shusen Tang, conceptualization, methodology, writing – review & editing, supervision.

 

Supporting Agencies

This work was supported by the Key Research Project of Wannan Medical College (Project No. WK2023ZZD15).

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.

 

How to Cite



1.
Xue Q, Feng G, Hu J, Li F, Tang S. Dopamine beta-hydroxylase mediates atherosclerosis progression by regulating copper metabolism via PHOX2A. Eur J Histochem [Internet]. 2026 Oct. 27 [cited 2026 Nov. 10];70(4). Available from: https://www.ejh.it/ejh/article/view/4586
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