ArticleChest2017
Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers.
Article in Chest, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01762774 (A Single-centre, Randomised, Double-blind, Placebo-controlled, Escalating Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2256294 in Healthy Volunteers, and Single and Repeat Doses of GSK2256294 in Adult Male Moderately Obese Smokers), which is not on this map. Cited by 46 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.
A Single-centre, Randomised, Double-blind, Placebo-controlled, Escalating Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2256294 in Healthy Volunteers, and Single and Repeat Doses of GSK2256294 in Adult Male Moderately Obese Smokers
Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- A Double-Blind, Randomized, Placebo-Controlled Trial of Soluble Epoxide Hydrolase Inhibition in Patients with Aneurysmal Subarachnoid Hemorrhage.Neurocritical care · 2022Trial
- GSK2256294 Decreases sEH (Soluble Epoxide Hydrolase) Activity in Plasma, Muscle, and Adipose and Reduces F2-Isoprostanes but Does Not Alter Insulin Sensitivity in Humans.Hypertension (Dallas, Tex. : 1979) · 2021Trial
- Epoxyeicosatrienoic acids protect airway epithelial mitochondria by activating the cAMP/PKA-DRP1 Ser637 axis in cigarette smoke-induced lung injury.Respiratory research · 2026Article
- Epoxy-oxylipins direct monocyte fate in inflammatory resolution in humans.Nature communications · 2026Article
- Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase.Journal of medicinal chemistry · 2025Article
- Article
- Impacts of zinc enriched spirulina as an adjunct to conventional treatment of patients with Chronic Obstructive Pulmonary Disease: Study protocol for a North African randomized controlled trial (SPIRICOPD).La Tunisie medicale · 2024Article
- High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.European radiology · 2024Article
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulation of soluble epoxide hydrolase in renal-associated diseases: insights from potential mechanisms to clinical researches.Frontiers in endocrinology · 2024Review
- Determinants of Meal-Induced Changes in Circulating FFA Epoxides, Diols, and Diol-to-Epoxide Ratios as Indices of Soluble Epoxide Hydrolase Activity.International journal of molecular sciences · 2023Article
- Small-molecule discovery through DNA-encoded libraries.Nature reviews. Drug discovery · 2023Review
- EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis.Redox biology · 2023Article
- Effects of Individual Circulating FFAs on Plasma and Hepatic FFA Epoxides, Diols, and Epoxide-Diol Ratios as Indices of Soluble Epoxide Hydrolase Activity.International journal of molecular sciences · 2023Article
- Association of CYP2C19 Polymorphic Markers with Cardiovascular Disease Risk Factors in Gas Industry Workers Undergoing Periodic Medical Examinations.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2023Article
- Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.Journal of the American Heart Association · 2023Article
- Soluble epoxide hydrolase inhibitors for smoking-associated inflammatory lung diseases and chronic obstructive pulmonary disease: a meta-analytical systematic review of preclinical and clinical studies.American journal of translational research · 2023Review
- Bioactive lipids in hypertension.Advances in pharmacology (San Diego, Calif.) · 2023Article
- High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundSmoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo.
methodsEndogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers.
resultsCompared with control groups, there was reduced vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 μM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% ± 4.2% vs 72.6% ± 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (-8.33 ± 0.172 logM vs -8.10 ± 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% ± 46% before a dose to 566% ± 110% after a single dose (P = .02) and to 503% ± 123% after a chronic dose (P = .003).
conclusionsGSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov.
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.