ArticleMolecular and cellular biochemistry2016
Ascorbic acid prevents VEGF-induced increases in endothelial barrier permeability.
Article in Molecular and cellular biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes.Scientific reports · 2021Trial
- Effects of ascorbic acid on trabecular meshwork gene expression and collagen secretion.BMJ open ophthalmology · 2026Article
- Protein nano-bioactives against microgravity-induced endothelial dysfunction.NPJ microgravity · 2026Article
- Human bone marrow-mesenchymal stem cells differentiation into brain-like endothelial cells.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- Luteolin alleviates angiogenesis in HUVECs by inhibiting VEGFA expression: integrating network pharmacology and experimental validation.Scientific reports · 2025Article
- Succinate Regulates Endothelial Mitochondrial Function and Barrier Integrity.Antioxidants (Basel, Switzerland) · 2024Article
- How Do Minerals, Vitamins, and Intestinal Microbiota Affect the Development and Progression of Heart Disease in Adult and Pediatric Patients?Nutrients · 2023Review
- Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Low Levels of Vitamin C during Pregnancy; a Risk Marker of Progression of Diabetic Retinopathy in Type 1 Diabetic Women?Antioxidants (Basel, Switzerland) · 2023Article
- Clofibrate, a Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride-Induced Toxicity.Biological trace element research · 2022Article
- Variable fluid flow regimes alter human brain microvascular endothelial cell-cell junctions and cytoskeletal structure.Cytoskeleton (Hoboken, N.J.) · 2021Article
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- Vitamin C and Cardiovascular Disease: An Update.Antioxidants (Basel, Switzerland) · 2020Review
- Transcriptional Correlates of Tolerance and Lethality in Mice Predict Ebola Virus Disease Patient Outcomes.Cell reports · 2020Article
- Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation.Oxidative medicine and cellular longevity · 2020Review
- Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology.Journal of diabetes research · 2019Review
- The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway.Oxidative medicine and cellular longevity · 2019Review
- Pressure-dependent NOS activation contributes to endothelial hyperpermeability in a model of acute heart failure.Bioscience reports · 2018Article
- Effects of uric acid on vascular endothelial function from bedside to bench.Hypertension research : official journal of the Japanese Society of Hypertension · 2018Article
- Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.Biochemical and biophysical research communications · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) increases endothelial barrier permeability, an effect that may contribute to macular edema in diabetic retinopathy. Since vitamin C, or ascorbic acid, can tighten the endothelial permeability barrier, we examined whether it could prevent the increase in permeability due to VEGF in human umbilical vein endothelial cells (HUVECs). As previously observed, VEGF increased HUVEC permeability to radiolabeled inulin within 60 min in a concentration-dependent manner. Loading the cells with increasing concentrations of ascorbate progressively prevented the leakage caused by 100 ng/ml VEGF, with a significant inhibition at 13 µM and complete inhibition at 50 µM. Loading cells with 100 µM ascorbate also decreased the basal generation of reactive oxygen species and prevented the increase caused by both 100 ng/ml VEGF. VEGF treatment decreased intracellular ascorbate by 25%, thus linking ascorbate oxidation to its prevention of VEGF-induced barrier leakage. The latter was blocked by treating the cells with 60 µM L-NAME (but not D-NAME) as well as by 30 µM sepiapterin, a precursor of tetrahydrobiopterin that is required for proper function of endothelial nitric oxide synthase (eNOS). These findings suggest that VEGF-induced barrier leakage uncouples eNOS. Ascorbate inhibition of the VEGF effect could thus be due either to scavenging superoxide or to peroxynitrite generated by the uncoupled eNOS, or more likely to its ability to recycle tetrahydrobiopterin, thus avoiding enzyme uncoupling in the first place. Ascorbate prevention of VEGF-induced increases in endothelial permeability opens the possibility that its repletion could benefit diabetic macular edema.
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