ArticleScientific reports2020
Context-dependent regulation of endothelial cell metabolism: differential effects of the PPARβ/δ agonist GW0742 and VEGF-A.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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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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.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Peroxisome Proliferator-Activated Receptor Delta (PPARδ) as a Metabolic Gatekeeper of Cerebrovascular Integrity.Journal of molecular neuroscience : MN · 2026Review
- Nanoparticle-Mediated PPAR Modulation of Macrophage Polarization in Radiation Enteritis: A Narrative Review.Drug design, development and therapy · 2026Review
- Mechanisms and therapeutics of immunometabolic reprogramming driving macrophage-ECs interactions in sepsis-associated ARDS from the gut-lung axis perspective.Frontiers in immunology · 2026Review
- Exploring Endothelial Cell Dysfunction's Impact on the Brain-Retina Microenvironment Connection: Molecular Mechanisms and Implications.Molecular neurobiology · 2025Review
- PPARs in Clinical Experimental Medicine after 35 Years of Worldwide Scientific Investigations and Medical Experiments.Biomolecules · 2024Review
- Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A.International journal of molecular sciences · 2024Article
- Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia.BMC medicine · 2024Article
- Role of autophagy in angiogenic potential of vascular pericytes.Frontiers in cell and developmental biology · 2024Review
- Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases.Investigative ophthalmology & visual science · 2023Review
- Article
- Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance.The EMBO journal · 2022Article
- Article
- Protective Effect ofOxidative medicine and cellular longevity · 2022Article
- Interferon-γ Impairs Human Coronary Artery Endothelial Glucose Metabolism by Tryptophan Catabolism and Activates Fatty Acid Oxidation.Circulation · 2021Article
- Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.Redox biology · 2021Article
- Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway.Frontiers in pharmacology · 2021Article
- PPARs and Angiogenesis-Implications in Pathology.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator activated receptor β/δ (PPARβ/δ) has pro-angiogenic functions, but whether PPARβ/δ modulates endothelial cell metabolism to support the dynamic phenotype remains to be established. This study characterised the metabolic response of HUVEC to the PPARβ/δ agonist, GW0742, and compared these effects with those induced by VEGF-A. In HUVEC monolayers, flux analysis revealed that VEGF-A promoted glycolysis at the expense of fatty acid oxidation (FAO), whereas GW0742 reduced both glycolysis and FAO. Only VEGF-A stimulated HUVEC migration and proliferation whereas both GW0742 and VEGF-A promoted tubulogenesis. Studies using inhibitors of PPARβ/δ or sirtuin-1 showed that the tubulogenic effect of GW0742, but not VEGF-A, was PPARβ/δ- and sirtuin-1-dependent. HUVEC were reliant on glycolysis and FAO, and inhibition of either pathway disrupted cell growth and proliferation. VEGF-A was a potent inducer of glycolysis in tubulogenic HUVEC, while FAO was maintained. In contrast, GW0742-induced tubulogenesis was associated with enhanced FAO and a modest increase in glycolysis. These novel data reveal a context-dependent regulation of endothelial metabolism by GW0742, where metabolic activity is reduced in monolayers but enhanced during tubulogenesis. These findings expand our understanding of PPARβ/δ in the endothelium and support the targeting of PPARβ/δ in regulating EC behaviour and boosting tissue maintenance and repair.
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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.