ArticleScientific reports2015
Copper Transport Protein Antioxidant-1 Promotes Inflammatory Neovascularization via Chaperone and Transcription Factor Function.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 129 citations in OpenAlex.
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Harnessing Cuproptosis for Antitumor Immunity: A Review of Current Evidence and Therapeutic Strategies.Molecular carcinogenesis · 2026Review
- Endothelial Drp1 integrates VEGF-induced redox signaling with glycolysis through cysteine oxidation to drive angiogenesis.Nature communications · 2026Article
- Review
- Cuproptosis and Its Impact on Cardiovascular Health: Mechanisms and Therapeutic Opportunities.Cardiovascular toxicology · 2026Review
- The Multifaceted Properties of Copper and Zinc in Skin Healing.Dermatology and therapy · 2026Article
- The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.Molecular and cellular biology · 2026Article
- The Yin and Yang of copper in cardiovascular health and disease.Molecular and cellular biochemistry · 2026Review
- Association of Copper with Atherosclerosis and Treatment Strategies.Journal of cardiovascular translational research · 2025Review
- Effect of a Reduced-Protein Diet Supplemented with Essential Amino Acids on the Muscle Proteome of Female and Entire Male Finishing Pigs.Animals : an open access journal from MDPI · 2025Article
- Novel Role of Copper Transporter CTR1 and Therapeutic Potential of Copper Chelators in Retinal Ischemia-Reperfusion Injury.Investigative ophthalmology & visual science · 2025Article
- Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension.The American journal of pathology · 2025Article
- Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Reprogramming of epidermal keratinocytes by PITX1 transforms the cutaneous cellular landscape and promotes wound healing.JCI insight · 2024Article
- Chaperone-Derived Copper(I)-Binding Peptide Nanofibers Disrupt Copper Homeostasis in Cancer Cells.Angewandte Chemie (International ed. in English) · 2024Article
- Roles of Copper Transport Systems Members in Breast Cancer.Cancer medicine · 2024Review
- Altered copper transport in oxidative stress-dependent brain endothelial barrier dysfunction associated with Alzheimer's disease.Vascular pharmacology · 2024Article
- Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.Metallomics : integrated biometal science · 2024Review
- The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.Cell communication and signaling : CCS · 2024Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Copper (Cu), an essential micronutrient, plays a fundamental role in inflammation and angiogenesis; however, its precise mechanism remains undefined. Here we uncover a novel role of Cu transport protein Antioxidant-1 (Atox1), which is originally appreciated as a Cu chaperone and recently discovered as a Cu-dependent transcription factor, in inflammatory neovascularization. Atox1 expression is upregulated in patients and mice with critical limb ischemia. Atox1-deficient mice show impaired limb perfusion recovery with reduced arteriogenesis, angiogenesis, and recruitment of inflammatory cells. In vivo intravital microscopy, bone marrow reconstitution, and Atox1 gene transfer in Atox1(-/-) mice show that Atox1 in endothelial cells (ECs) is essential for neovascularization and recruitment of inflammatory cells which release VEGF and TNFα. Mechanistically, Atox1-depleted ECs demonstrate that Cu chaperone function of Atox1 mediated through Cu transporter ATP7A is required for VEGF-induced angiogenesis via activation of Cu enzyme lysyl oxidase. Moreover, Atox1 functions as a Cu-dependent transcription factor for NADPH oxidase organizer p47phox, thereby increasing ROS-NFκB-VCAM-1/ICAM-1 expression and monocyte adhesion in ECs inflamed with TNFα in an ATP7A-independent manner. These findings demonstrate a novel linkage between Atox1 and NADPH oxidase involved in inflammatory neovascularization and suggest Atox1 as a potential therapeutic target for treatment of ischemic disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.