ArticleOncotarget2017
Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Trial
- VHL Suppresses Angiogenesis Through HIF-1a-Mediated Ang/Tie2/AMPK/VEGF Signaling Pathway in Tie-2 Expressed Macrophages (TEMs).Biochemical genetics · 2026Article
- Metformin and the Development of Age-Related Macular Degeneration.JAMA ophthalmology · 2025Article
- Exploring the Protective Effects of Traditional Antidiabetic Medications and Novel Antihyperglycemic Agents in Diabetic Rodent Models.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.Frontiers in pharmacology · 2025Article
- New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis.Biomolecules & therapeutics · 2025Review
- Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.International journal of molecular sciences · 2024Article
- Role of Leptin and Adiponectin in Carcinogenesis.Cancers · 2023Review
- Obesity induces adipose fibrosis and collagen cross-linking through suppressing AMPK and enhancing lysyl oxidase expression.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Review
- Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Rethinking growth factors: the case of BMP9 during vessel maturation.Vascular biology (Bristol, England) · 2022Review
- Metformin suppresses proliferation and differentiation induced by BMP9Frontiers in pharmacology · 2022Article
- Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology.Pharmaceutics · 2021Article
- Article
- Newly-found functions of metformin for the prevention and treatment of age-related macular degeneration.International journal of ophthalmology · 2021Review
- Metformin: The next angiogenesis panacea?SAGE open medicine · 2021Review
- Metformin coordinates osteoblast/osteoclast differentiation associated with ischemic osteonecrosis.Aging · 2020Article
- E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease.International journal of biological sciences · 2020Review
- The Roles of AMPK in Revascularization.Cardiology research and practice · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9. This event was mimicked by expression of the active mutant of AMPKα1 and prevented by the dominant negative AMPKα1. Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1. Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel plug. In addition, laser photocoagulation was employed to evaluate the effect of metformin. The data revealed that metformin significantly reduced choroidal neovascularization to a level comparable to LDN212854, an ALK1 specific inhibitor. In conjunction, metformin diminished expression of ALK1 in endothelium of the lesion area. Collectively, our study for the first time demonstrates that AMPK inhibits ALK1 and associated angiogenesis/neovascularization. This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.