ReviewNitric oxide : biology and chemistry2011
Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease.
Review in Nitric oxide : biology and chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- Efficacy of folic acid supplementation in the prevention of cardiovascular disease - a systematic review and meta-analysis of randomized controlled trials.BMC nutrition · 2025Pooled it
- Pooled it
- No effect of acute tetrahydrobiopterin (BHJournal of applied physiology (Bethesda, Md. : 1985) · 2022Trial
- Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans.American journal of physiology. Heart and circulatory physiology · 2017Trial
- Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms.Clinical science (London, England : 1979) · 2015Trial
- Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: association with disease severity.PLoS pathogens · 2015Trial
- Trial
- Hydroxyhydroquinone as a novel modulator of mitochondrial metabolism with potential to restore CoQ10 homeostasis.Molecular and cellular biochemistry · 2026Article
- DASH Diet, Dietary Nitrate, and Nitric Oxide Bioavailability: Implications for Endothelial Dysfunction and Hypertension in Older Adults.Molecular nutrition & food research · 2026Review
- Folic Acid and Endothelial Dysfunction in COVID-19.Life (Basel, Switzerland) · 2026Review
- Role of L-Arginine and Tetrahydrobiopterin in Attenuation of Vascular Ang1-8 Reactivity via Endothelial PI3K/AKT/eNOS Signaling Pathways in HgCl2-Induced Vascular Dysfunction. An Ex-Vivo Study.Cardiovascular toxicology · 2026Article
- From probiotic depletion to inflammatory cascade: multi-omics reveals the temporal progression of sleep deprivation-induced gut-liver axis disruption in mice.Frontiers in microbiology · 2026Article
- Mechanism of auranofin toxicity: Inhibition of tetrahydrobiopterin metabolism.Toxicology and applied pharmacology · 2026Article
- QDPR rs3733570 polymorphism is associated with type 2 diabetes and diabetic kidney disease accompanied by hyperlipidemia in the Chinese Han population.Frontiers in medicine · 2026Article
- Pathological mechanisms and clinical research progress of endothelial dysfunction.Frontiers in cardiovascular medicine · 2026Review
- Green tea's secret weapon: a review on the protective effects of epigallocatechin-3-gallate against ischemia/reperfusion damage.Pharmacological reports : PR · 2025Review
- Ferroptosis: a potential target for non-surgical treatment of laryngeal cancer.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Review
- HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.Neuroscience bulletin · 2025Article
- Advanced treatment strategies for high-altitude pulmonary hypertension employing natural medicines: A review.Journal of pharmaceutical analysis · 2025Review
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nitric oxide, generated by the nitric oxide synthase (NOS) enzymes, plays pivotal roles in cardiovascular homeostasis and in the pathogenesis of cardiovascular disease. The NOS cofactor, tetrahydrobiopterin (BH4), is an important regulator of NOS function, since BH4 is required to maintain enzymatic coupling of L-arginine oxidation, to produce NO. Loss or oxidation of BH4 to 7,8-dihydrobiopterin (BH2) is associated with NOS uncoupling, resulting in the production of superoxide rather than NO. In addition to key roles in folate metabolism, dihydrofolate reductase (DHFR) can 'recycle' BH2, and thus regenerate BH4. It is therefore likely that net BH4 cellular bioavailability reflects the balance between de novo BH4 synthesis, loss of BH4 by oxidation to BH2, and the regeneration of BH4 by DHFR. Recent studies have implicated BH4 recycling in the direct regulation of eNOS uncoupling, showing that inhibition of BH4 recycling using DHFR-specific siRNA and methotrexate treatment leads to eNOS uncoupling in endothelial cells and the hph-1 mouse model of BH4 deficiency, even in the absence of oxidative stress. These studies indicate that not only BH4 level, but the recycling pathways regulating BH4 bioavailability represent potential therapeutic targets and will be discussed in this review.
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What OpenQuestion holds
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.