Trial reportCirculation2011
Induction of vascular GTP-cyclohydrolase I and endogenous tetrahydrobiopterin synthesis protect against inflammation-induced endothelial dysfunction in human atherosclerosis.
Trial report in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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
31 citing papers in PubMed, 71 citations in OpenAlex.
- A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness.AIDS (London, England) · 2015Trial
- Effect of cardiorespiratory fitness on acute inflammation induced increases in arterial stiffness in older adults.European journal of applied physiology · 2013Trial
- Folic Acid and Endothelial Dysfunction in COVID-19.Life (Basel, Switzerland) · 2026Review
- Association between circulating GTP cyclohydrolase 1 concentrations and acute ischemic stroke: an exploratory case-control study in a Chinese population.Frontiers in neurology · 2026Article
- Mitigating atherosclerosis: Integrating vaccines with gene targets.American heart journal plus : cardiology research and practice · 2025Review
- Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.Life science alliance · 2024Article
- Dynamic A-to-I RNA editing during acute neuroinflammation in sepsis-associated encephalopathy.Frontiers in neuroscience · 2024Article
- Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.bioRxiv : the preprint server for biology · 2023Article
- Neopterin, the Cell-Mediated Immune Response Biomarker, in Inflammatory Periodontal Diseases: A Narrative Review of a More than Fifty Years Old Biomarker.Biomedicines · 2023Review
- Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.The Journal of clinical investigation · 2022Article
- A StandardizedPlants (Basel, Switzerland) · 2021Article
- Oral vitamin C restores endothelial function during acute inflammation in young and older adults.Physiological reports · 2021Article
- Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry.Current neuropharmacology · 2021Review
- GCH1 haplotypes and cardiovascular risk in HIV.AIDS (London, England) · 2019Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in DiabeticInternational journal of endocrinology · 2018Article
- 'Browning' the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk.International journal of cardiology · 2017Review
- Tetrahydrobiopterin Protects Against Hypertrophic Heart Disease Independent of Myocardial Nitric Oxide Synthase Coupling.Journal of the American Heart Association · 2016Article
- Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.Anesthesiology · 2015Article
- Reply: Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.Brain : a journal of neurology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) is essential for maintenance of enzymatic function. We hypothesized that induction of BH4 synthesis might be an endothelial defense mechanism against inflammation in vascular disease states. METHODS AND
resultsIn Study 1, 20 healthy individuals were randomized to receive Salmonella typhi vaccine (a model of acute inflammation) or placebo in a double-blind study. Vaccination increased circulating BH4 and interleukin 6 and induced endothelial dysfunction (as evaluated by brachial artery flow-mediated dilation) after 8 hours. In Study 2, a functional haplotype (X haplotype) in the GCH1 gene, encoding GTP-cyclohydrolase I, the rate-limiting enzyme in biopterin biosynthesis, was associated with endothelial dysfunction in the presence of high-sensitivity C-reactive protein in 440 coronary artery disease patients. In Study 3, 10 patients with coronary artery disease homozygotes for the GCH1 X haplotype (XX) and 40 without the haplotype (OO) underwent S Typhi vaccination. XX patients were unable to increase plasma BH4 and had a greater reduction of flow-mediated dilation than OO patients. In Study 4, vessel segments from 19 patients undergoing coronary bypass surgery were incubated with or without cytokines (interleukin-6/tumor necrosis factor-α/lipopolysaccharide) for 24 hours. Cytokine stimulation upregulated GCH1 expression, increased vascular BH4, and improved vasorelaxation in response to acetylcholine, which was inhibited by the GTP-cyclohydrolase inhibitor 2,4-diamino-6-hydroxypyrimidine.
conclusionsThe ability to increase vascular GCH1 expression and BH4 synthesis in response to inflammation preserves endothelial function in inflammatory states. These novel findings identify BH4 as a vascular defense mechanism against inflammation-induced endothelial dysfunction.
Indexed as
Identifiers
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.