ArticleCellular and molecular life sciences : CMLS2021
eNOS controls angiogenic sprouting and retinal neovascularization through the regulation of endothelial cell polarity.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- The role of endothelial colony forming cells in the treatment of limb ischaemia: challenges in clinical translation.Stem cells translational medicine · 2026Review
- Review
- An atlas of cGAS-STING signaling in pathophysiological angiogenesis and retinal vascular homeostasis across species.Molecular therapy. Nucleic acids · 2026Article
- Glutathione responsive iNOS inhibiting polymeric prodrug for targeted Inhibition of angiogenesis.Journal of nanobiotechnology · 2026Article
- Bone-Targeting Microspheres Enable Sustained Release of CD301bTheranostics · 2026Article
- Inhibition of pathological angiogenesis in oxygen-induced retinopathy by arginine depletion with ADI-PEG20.Experimental eye research · 2026Article
- Physicochemical Characterization, Cytotoxicity, and In Vivo Evaluation of a Hydroxyapatite-Silver Composite for Bone Regeneration.BioMed research international · 2026Article
- Point-of-care treatment of acute skin wound by portable in-situ electrospinning nanofiber dressings with rapid hemostasis, anti-infection, and angiogenesis effects.Bioactive materials · 2025Article
- Targeting proteostasis pathways for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Endothelial Arginine Metabolism in Angiogenesis: Mechanistic Insights from Tissue Repair to Tumor Progression.Metabolites · 2025Review
- MY-1 promotes angiogenesis in the ischemic hindlimbs by regulating the stability of CDC42 via PSMD14.Angiogenesis · 2025Article
- Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia.International journal of molecular sciences · 2025Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy.Nature communications · 2025Article
- miR-486-5p Inhibits eNOS and Angiogenesis in Cultured Endothelial Cells by Targeting MAML3.Journal of cellular and molecular medicine · 2025Article
- CAVIN3 deficiency promotes vascular normalization in ocular neovascular disease via ERK/JAG1 signaling pathway.JCI insight · 2025Article
- Fibronectin Mediates Endothelial-to-Mesenchymal Transition in Retina Angiogenesis.Investigative ophthalmology & visual science · 2025Article
- Zinc sulfate gel reshapes the wound microenvironment to promote full-thickness wound healing in mice.Regenerative therapy · 2025Article
- Citrulline Plus Arginine Induces an Angiogenic Response and Increases Permeability in Retinal Endothelial Cells via Nitric Oxide Production.International journal of molecular sciences · 2025Article
- YBX1-driven TUBB6 upregulation facilitates ocular angiogenesis via WNT3A-FZD8 pathway.Theranostics · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The roles of nitric oxide (NO) and endothelial NO synthase (eNOS) in the regulation of angiogenesis are well documented. However, the involvement of eNOS in the sprouting of endothelial tip-cells at the vascular front during sprouting angiogenesis remains poorly defined. In this study, we show that downregulation of eNOS markedly inhibits VEGF-stimulated migration of endothelial cells but increases their polarization, as evidenced by the reorientation of the Golgi in migrating monolayers and by the fewer filopodia on tip cells at ends of sprouts in endothelial cell spheroids. The effect of eNOS inhibition on EC polarization was prevented in Par3-depleted cells. Importantly, downregulation of eNOS increased the expression of polarity genes, such as PARD3B, PARD6A, PARD6B, PKCΖ, TJP3, and CRB1 in endothelial cells. In retinas of eNOS knockout mice, vascular development is retarded with decreased vessel density and vascular branching. Furthermore, tip cells at the extremities of the vascular front have a marked reduction in the number of filopodia per cell and are more oriented. In a model of oxygen-induced retinopathy (OIR), eNOS deficient mice are protected during the initial vaso-obliterative phase, have reduced pathological neovascularization, and retinal endothelial tip cells have fewer filopodia. Single-cell RNA sequencing of endothelial cells from OIR retinas revealed enrichment of genes related to cell polarity in the endothelial tip-cell subtype of eNOS deficient mice. These results indicate that inhibition of eNOS alters the polarity program of endothelial cells, which increases cell polarization, regulates sprouting angiogenesis and normalizes pathological neovascularization during retinopathy.
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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.