ArticleNature communications2021
The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
54 citing papers in PubMed, 99 citations in OpenAlex.
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Endothelial Drp1 integrates VEGF-induced redox signaling with glycolysis through cysteine oxidation to drive angiogenesis.Nature communications · 2026Article
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- A Universal Metal-Flavonoid Coating Strategy: Engineering Biomaterials for Diabetic Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cuproptosis and Its Impact on Cardiovascular Health: Mechanisms and Therapeutic Opportunities.Cardiovascular toxicology · 2026Review
- Copper Nanocluster-Decorated Magnesium Silicate-Based Microneedle Enhances Antimicrobial Effects and Tissue Remodeling for Diabetic Wounds.Small science · 2026Article
- The Yin and Yang of copper in cardiovascular health and disease.Molecular and cellular biochemistry · 2026Review
- Harnessing copper: Innovative approaches to combat neurodegenerative diseases and cancer (Review).International journal of molecular medicine · 2026Review
- Targeting autophagy in dysfunctional tumor vasculature.iScience · 2025Review
- Cuproptosis and Cardiovascular Diseases: Mechanisms, Pathophysiology, and Therapeutic Strategies-A Narrative Review.Reviews in cardiovascular medicine · 2025Review
- Nanoparticles induced cuproptosis to enhance antitumor immunotherapy.Journal of nanobiotechnology · 2025Review
- Integrating cuproptosis and immunosenescence: A novel therapeutic strategy in cancer treatment.Biochemistry and biophysics reports · 2025Review
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system.Cancer pathogenesis and therapy · 2025Review
- Potential role of hypobaric hypoxia environment in treating pan-cancer.Scientific reports · 2025Article
- Paeoniflorin Attenuates Limb Ischemia by Promoting Angiogenesis Through ERα/ROCK-2 Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
VEGFR2 (KDR/Flk1) signaling in endothelial cells (ECs) plays a central role in angiogenesis. The P-type ATPase transporter ATP7A regulates copper homeostasis, and its role in VEGFR2 signaling and angiogenesis is entirely unknown. Here, we describe the unexpected crosstalk between the Copper transporter ATP7A, autophagy, and VEGFR2 degradation. The functional significance of this Copper transporter was demonstrated by the finding that inducible EC-specific ATP7A deficient mice or ATP7A-dysfunctional ATP7Amut mice showed impaired post-ischemic neovascularization. In ECs, loss of ATP7A inhibited VEGF-induced VEGFR2 signaling and angiogenic responses, in part by promoting ligand-induced VEGFR2 protein degradation. Mechanistically, VEGF stimulated ATP7A translocation from the trans-Golgi network to the plasma membrane where it bound to VEGFR2, which prevented autophagy-mediated lysosomal VEGFR2 degradation by inhibiting autophagic cargo/adapter p62/SQSTM1 binding to ubiquitinated VEGFR2. Enhanced autophagy flux due to ATP7A dysfunction in vivo was confirmed by autophagy reporter CAG-ATP7Amut -RFP-EGFP-LC3 transgenic mice. In summary, our study uncovers a novel function of ATP7A to limit autophagy-mediated degradation of VEGFR2, thereby promoting VEGFR2 signaling and angiogenesis, which restores perfusion recovery and neovascularization. Thus, endothelial ATP7A is identified as a potential therapeutic target for treatment of ischemic cardiovascular diseases.
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