ArticleThe Journal of clinical investigation1998
Nitric oxide synthase modulates angiogenesis in response to tissue ischemia.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 341 papers.
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Who cites it
341 citing papers in PubMed, 1,194 citations in OpenAlex.
- Da chuanxiong formula improves vascular remodeling via promoting angiogenesis and vasodilation mediated by PI3K/Akt/eNOS signaling.Metabolic brain disease · 2026Article
- RNF213 in Panvascular Disease: A Molecular Hub Linking Genetic Susceptibility to Systemic Vasculopathy.Biomedicines · 2026Review
- Nitration in cancer signaling.Redox biology · 2026Review
- Clopidogrel bisulfate modulates metabolic activity and ERK-associated signaling in human endothelial progenitor cells under oxidative stress: an in vitro study.Scientific reports · 2026Article
- The HCMV-encoded miR-UL36-3p promotes angiogenesis of endothelial cells by downregulating FOXO3.Animal models and experimental medicine · 2026Article
- CS-NO releasing hydrogel protects against neuron apoptosis and inflammation through suppressing the HIF-1α and MAPK pathway in stroke.Materials today. Bio · 2026Article
- Treatment with Sildenafil Promotes Angiogenesis and Modulates Immune Response in Ischemic Muscle Tissue.Current issues in molecular biology · 2026Article
- The Heart in Space: Effects of Microgravity on Different Cell Types and Their Functions in the Cardiovascular System.Biomedicines · 2025Review
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Angiogenesis: Biological Mechanisms and In Vitro Models.Annals of biomedical engineering · 2025Review
- Loss of CD98HC phosphorylation by ATM impairs antiporter trafficking and drives glutamate toxicity in Ataxia telangiectasia.Nature communications · 2025Article
- Review
- Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies.Biomarker research · 2025Review
- Biomaterial-based vascularization strategies for enhanced treatment of peripheral arterial disease.Journal of nanobiotechnology · 2025Review
- Article
- The Extremely-Low-Frequency Electromagnetic Field Affects Apoptosis and Oxidative-Stress-Related Genes and Proteins in the Porcine Endometrium-An In Vitro Study.International journal of molecular sciences · 2024Article
- Chronic circadian rhythm disorder induces heart failure with preserved ejection fraction-like phenotype through the Clock-sGC-cGMP-PKG1 signaling pathway.Scientific reports · 2024Article
- Nitric Oxide Releasing Nanomaterials for Cardiovascular Applications.JACC. Basic to translational science · 2024Review
- The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID).International journal of molecular sciences · 2024Review
- Effect of a protein kinase B (Akt) inhibitor on the angiogenesis of HUVECs and corneal neovascularization.Wiener klinische Wochenschrift · 2024Article
281 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates angiogenesis in two animal models in which therapeutic angiogenesis has been characterized as a compensatory response to tissue ischemia. We first administered L-arginine, previously shown to augment endogenous production of NO, to normal rabbits with operatively induced hindlimb ischemia. Angiogenesis in the ischemic hindlimb was significantly improved by dietary supplementation with L-arginine, compared to placebo-treated controls; angiographically evident vascularity in the ischemic limb, hemodynamic indices of limb perfusion, capillary density, and vasomotor reactivity in the collateral vessel-dependent ischemic limb were all improved by oral L-arginine supplementation. A murine model of operatively induced hindlimb ischemia was used to investigate the impact of targeted disruption of the gene encoding for ENOS on angiogenesis. Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS-/- mice versus wild-type controls evaluated by either laser Doppler flow analysis or capillary density measurement. Impaired angiogenesis in eNOS-/- mice was not improved by administration of vascular endothelial growth factor (VEGF), suggesting that eNOS acts downstream from VEGF. Thus, (a) eNOS is a downstream mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine supplementation accelerates in vivo angiogenesis. These findings suggest that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation constitutes a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction.
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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.