ArticleBrain research2012
PPARδ agonist GW501516 prevents uncoupling of endothelial nitric oxide synthase in cerebral microvessels of hph-1 mice.
Article in Brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.Journal of advanced research · 2025Review
- Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Review
- Characterization of cerebral microvasculature in transgenic mice with endothelium targeted over-expression of GTP-cyclohydrolase I.Brain research · 2015Article
- Uncoupling of endothelial nitric oxide synthase in cerebral vasculature of Tg2576 mice.Journal of neurochemistry · 2015Article
- The COP9 signalosome and vascular function: intriguing possibilities?American journal of cardiovascular disease · 2015Review
- Erythropoietin prevents endothelial dysfunction in GTP-cyclohydrolase I-deficient hph1 mice.Journal of cardiovascular pharmacology · 2014Article
- Erythropoietin increases bioavailability of tetrahydrobiopterin and protects cerebral microvasculature against oxidative stress induced by eNOS uncoupling.Journal of neurochemistry · 2014Article
- Mechanisms of vascular dysfunction in mice with endothelium-specific deletion of the PPAR-δ gene.American journal of physiology. Heart and circulatory physiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Peroxisome proliferator-activated receptor delta (PPARδ) is ubiquitously expressed in the vasculature, including cerebral circulation. The role of PPARδ in metabolism of tetrahydrobiopterin (BH₄) has not been studied in the cerebral microvasculature. In the present study, the effects of PPARδ agonist GW501516 on uncoupling of endothelial nitric oxide synthase (eNOS) were determined in cerebral microvessels of BH₄-deficient hph-1 mice. Wild-type (B6CBA) and hph-1 mice were orally gavaged with a selective PPARδ activator, GW501516 (2 mg/kg/day) for 14 days, and thereafter, cerebral microvessels were isolated and studied. Treatment of hph-1 mice with GW501516 significantly reduced oxidation of BH₄ and increased the ratio of BH₄ to 7,8-BH₂ (P<0.05, n=6-9). Attenuation of L-NAME-inhibitable superoxide anion levels by GW501516 demonstrated that activation of PPARδ might prevent uncoupling of endothelial nitric oxide synthase (eNOS, P<0.05, n=6-9). Western blotting studies demonstrated that GW501516 selectively increased the endothelial expressions of CuZn superoxide dismutase (P<0.05, n=6-9) and catalase (P<0.05, n=6-8). PPARδ activation increased the total nitrite and nitrate (NO₂+NO₃) content in cerebral microvessels (P<0.05, n=6). Obtained results suggest that in vivo activation of PPARδ prevents eNOS uncoupling, restores bioavailability of NO and may help preserve endothelial function in the BH₄-deficient cerebral circulation.
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.