ArticleProceedings of the National Academy of Sciences of the United States of America2005
Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 4 of them syntheses that pooled it.
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Who cites it
136 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Maternal uric acid levels and risk of gestational diabetes mellitus: A systematic review and dose-response meta-analysis of cohort studies including 105,380 participants.Journal of diabetes investigation · 2023Pooled it
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- Effects of Repeated-Sprint Training in Hypoxia on Sea-Level Performance: A Meta-Analysis.Sports medicine (Auckland, N.Z.) · 2017Pooled it
- Effects of Exercise Training in Hypoxia Versus Normoxia on Vascular Health.Sports medicine (Auckland, N.Z.) · 2016Pooled it
- Integrated Analysis of Rat Pulmonary Hypertension Datasets Identifies Candidate circRNA Networks in Hypoxia-Exposed Pulmonary Artery Tissue.International journal of molecular sciences · 2026Article
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- CD47 and FOXP3Cancers · 2026Review
- Glyceryl Trinitrate Enhances Caffeine Cytotoxicity Under Metabolic Stress in Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- Article
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- Association between serum uric acid and the risk of gestational diabetes mellitus: a multicenter cohort study.Frontiers in nutrition · 2026Article
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats.Toxicology research · 2025Article
- Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects.Bioactive materials · 2025Article
- Angiogenesis: Biological Mechanisms and In Vitro Models.Annals of biomedical engineering · 2025Review
- The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?Molecules (Basel, Switzerland) · 2025Review
- Shear Stress Regulates Osteogenic Differentiation of Human Dental Pulp Stem Cells via the p38 Pathway.International journal of molecular sciences · 2025Article
- Ultrasound-Responsive 4D Bioscaffold for Synergistic Sonopiezoelectric-Gaseous Osteosarcoma Therapy and Enhanced Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- miR-486-5p Inhibits eNOS and Angiogenesis in Cultured Endothelial Cells by Targeting MAML3.Journal of cellular and molecular medicine · 2025Article
- Wound state monitoring by multiplexed, electrochemical, real-time, localized, inflammation-tracking nitric oxide sensor (MERLIN).Science advances · 2025Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Nitric oxide (NO) donors have been shown to stimulate and inhibit the proliferation, migration, and differentiation of endothelial cells in vitro and angiogenesis in vivo. Recently, we have shown distinct thresholds for NO to regulate p53-Ser-15P, phosphorylated extracellular signal-regulated kinase (pERK), and hypoxia inducible factor 1alpha in tumor cells. Because these signaling pathways also promote the growth and survival of endothelial cells, we examined their roles in angiogenic responses of venous endothelial cells and vascular outgrowth of muscle explants elicited by NO. An additional protein involved in the regulation of angiogenesis is thrombospondin-1 (TSP1), a matricellular glycoprotein known to influence adhesion, migration, and proliferation of endothelial cells. Here we demonstrate a triphasic regulation of TSP1 mediated by a slow and prolonged release of NO that depends on ERK phosphorylation. Under conditions of 5% serum, a 24-h exposure of NO donor (0.1-1,000 microM) mediated a triphasic response in the expression of TSP1 protein: decreasing at 0.1 microM, rebounding at 100 microM, and decreasing again at 1,000 microM. Under the same conditions, we observed a dose-dependent increase in P53 phosphorylation and inverse biphasic responses of pERK and mitogen-activated protein kinase phosphatase-1. Both the growth-stimulating activity of low-dose NO for endothelial cells and suppression of TSP1 expression were ERK-dependent. Conversely, exogenous TSP1 suppressed NO-mediated pERK. These results suggest that dose-dependent positive- and negative-feedback loops exist between NO and TSP1. Limiting TSP1 expression by positive feedback through the ERK mitogen-activated protein kinase pathway may facilitate switching to a proangiogenic state at low doses of NO.
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