ArticleEMBO molecular medicine2017
Intracellular adenosine regulates epigenetic programming in endothelial cells to promote angiogenesis.
Article in EMBO molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
- Ethanol Alters DNMT1/3a/3b Expression Profile, Promotes Persistent DNA Hypomethylation in Human Brain Endothelial Cells and Impairs Late Cortical Angiogenesis.Journal of neurochemistry · 2026Article
- Spatiotemporal dynamics of ecto-5'-nucleotidase (CD73) in mouse retina under physiological conditions.Development (Cambridge, England) · 2026Article
- Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development.International journal of molecular sciences · 2025Article
- Targeting adenosine APurinergic signalling · 2025Review
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- Adenosine Monophosphate Improves Lipolysis in Obese Mice by Reducing DNA Methylation via ADORA2A Activation by Ecto-5'-Nucleotidase (CD73).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.Frontiers of medicine · 2025Article
- Mission SpaceX CRS-16 RRRM-1 space flight induced skin genomic plasticity via an epigenetic trigger.iScience · 2024Article
- Extracellular adenosine oppositely regulates the purinome machinery in glioblastoma and mesenchymal stem cells.IUBMB life · 2024Article
- Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- A1 adenosine receptor antagonist induces cell apoptosis in KYSE-30 and YM-1 esophageal cancer cell lines.BioMedicine · 2023Article
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
- Adenosine kinase promotes post-infarction cardiac repair by epigenetically maintaining reparative macrophage phenotype.Journal of molecular and cellular cardiology · 2023Article
- Suppression of myeloid PFKFB3-driven glycolysis protects mice from choroidal neovascularization.British journal of pharmacology · 2022Article
- Gene-dosage effect of Pfkfb3 on monocyte/macrophage biology in atherosclerosis.British journal of pharmacology · 2022Article
- CoClBiomedicines · 2022Article
- Adenosine-Metabolizing Enzymes, Adenosine Kinase and Adenosine Deaminase, in Cancer.Biomolecules · 2022Review
- Potential epigenetic molecular regulatory networks in ocular neovascularization.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the levels of intracellular adenosine in human endothelial cells. Knockdown (KD) of ADK elevated intracellular adenosine, promoted proliferation, migration, and angiogenic sprouting in human endothelial cells. Additionally, mice deficient in endothelial ADK displayed increased angiogenesis as evidenced by the rapid development of the retinal and hindbrain vasculature, increased healing of skin wounds, and prompt recovery of arterial blood flow in the ischemic hindlimb. Mechanistically, hypomethylation of the promoters of a series of pro-angiogenic genes, especially for VEGFR2 in ADK KD cells, was demonstrated by the Infinium methylation assay. Methylation-specific PCR, bisulfite sequencing, and methylated DNA immunoprecipitation further confirmed hypomethylation in the promoter region of VEGFR2 in ADK-deficient endothelial cells. Accordingly, loss or inactivation of ADK increased VEGFR2 expression and signaling in endothelial cells. Based on these findings, we propose that ADK downregulation-induced elevation of intracellular adenosine levels in endothelial cells in the setting of hypoxia is one of the crucial intrinsic mechanisms that promote angiogenesis.
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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.