ArticleJournal of diabetes and its complications
Prevention of VEGF-induced growth and tube formation in human retinal endothelial cells by aldose reductase inhibition.
Article in Journal of diabetes and its complications. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
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- Customized Heparinized Alginate and Collagen Hydrogels for Tunable, Local Delivery of Angiogenic Proteins.ACS biomaterials science & engineering · 2025Article
- Prospects and limitations of cumate-inducible lentivirus as a tool for investigating VEGF-A-mediated pathology in diabetic retinopathy.Scientific reports · 2024Article
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- Vitamin DFrontiers in pharmacology · 2022Article
- A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway.Bioactive materials · 2021Article
- Article
- Role of aldose reductase in diabetes-induced retinal microglia activation.Chemico-biological interactions · 2019Article
- Didymin prevents hyperglycemia-induced human umbilical endothelial cells dysfunction and death.Biochemical pharmacology · 2018Article
- Endothelial Cell Metabolism.Physiological reviews · 2018Review
- Metabolic Regulation of Angiogenesis in Diabetes and Aging.Physiology (Bethesda, Md.) · 2017Review
- Aspalatone Prevents VEGF-Induced Lipid Peroxidation, Migration, Tube Formation, and Dysfunction of Human Aortic Endothelial Cells.Oxidative medicine and cellular longevity · 2017Article
- Gedunin abrogates aldose reductase, PI3K/Akt/mToR, and NF-κB signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease.EMBO molecular medicine · 2014Review
- Aldo-Keto Reductases: Multifunctional Proteins as Therapeutic Targets in Diabetes and Inflammatory Disease.Advances in experimental medicine and biologyReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSince diabetes-induced vascular endothelial growth factor (VEGF) is implicated in retinal angiogenesis, we aimed to examine the role of aldose reductase (AR) in VEGF-induced human retinal endothelial cells (HREC) growth and tube formation. MATERIALS AND
methodsHRECs were stimulated with VEGF and cell-growth was determined by MTT assay. AR inhibitor, fidarestat, to block the enzyme activity and AR siRNA to ablate AR gene expression in HREC were used to investigate the role of AR in neovascularization using cell-migration and tube formation assays. Various signaling intermediates and angiogenesis markers were assessed by Western blot analysis. Immuno-histochemical analysis of diabetic rat eyes was performed to examine VEGF expression in the retinal layer.
resultsStimulation of primary HREC with VEGF caused increased cell growth and migration, and AR inhibition with fidarestat or ablation with siRNA significantly prevented it. VEGF-induced tube formation in HREC was also significantly prevented by fidarestat. Treatment of HREC with VEGF also increased the expression of VCAM, AR, and phosphorylation and activation of Akt and p38-MAP kinase, which were prevented by fidarestat. VEGF-induced expression of VEGFRII in HREC was also prevented by AR inhibition or ablation.
conclusionsOur results indicate that inhibition of AR in HREC prevents tube formation by inhibiting the VEGF-induced activation of the Akt and p38-MAPK pathway and suggest a mediatory role of AR in ocular neovascularization generally implicated in retinopathy and AMD.
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