ArticleThe Journal of pharmacology and experimental therapeutics2007
peroxisome proliferator-activated receptor alpha activation-mediated regulation of endothelin-1 production via nitric oxide and protein kinase C signaling pathways in piglet cerebral microvascular endothelial cell culture.
Article in The Journal of pharmacology and experimental therapeutics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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.
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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.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Blood-Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2022Review
- Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Variants and expression changes in PPAR-encoding genes display no significant association with schizophrenia.Bioscience reports · 2020Observational
- Impact of the Renin-Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives.International journal of molecular sciences · 2020Review
- PPAR-α Agonist Fenofibrate Decreased RANTES Levels in Type 2 Diabetes Patients with Hypertriglyceridemia.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Kolaviron, Biflavonoid Complex from the Seed of Garcinia kola Attenuated Angiotensin II- and Lypopolysaccharide-induced Vascular Smooth Muscle Cell Proliferation and Nitric Oxide Production.Pharmacognosy research · 2016Article
- Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke.Neural regeneration research · 2015Review
- Fenofibrate subcellular distribution as a rationale for the intracranial delivery through biodegradable carrier.Journal of physiology and pharmacology : an official journal of the Polish Physiological Society · 2015Article
- PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia.PPAR research · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Elevated endothelin (ET)-1 has been implicated in cerebrovascular complications following brain trauma characterized by dysregulation of endothelial nitric oxide synthase (eNOS), protein kinase C (PKC), and cerebral function. Recently, vascular expression of PPARalpha has been observed and suggested to improve vascular dysfunction. We speculate that activation of PPARalpha in cerebral microvessels can improve cerebral dysfunction following trauma, and we tested the hypothesis that activation of cerebral endothelial peroxisome proliferator-activated receptor (PPAR)alpha will attenuate ET-1 production via a mechanism involving nitric oxide (NO) and PKC. Phorbol 12-myristate 13-acetate (PMA) (1 microM), bradykinin (BK, 1 microM), angiotensin II (AII, 1 microM), or hemoglobin (Hem, 10 microM) increased ET-1 levels by 24-, 11.4-, 3.6-, or 1.3-fold increasing ET-1 levels from 0.36 +/- 0.08 to 8.6 +/- 0.8, 4.1 +/- 0.7, 1.30 +/- 0.1, or 0.47 +/- 0.03 fmol/microg protein (p < 0.05), respectively. Clofibrate (10 microM) reduced basal ET-1 from 0.36 +/- 0.08 (control) to 0.03 +/- 0.01 and blunted vasoactive agent-induced increase to 0.12 +/- 0.07 (PMA), 0.6 +/- 0.04 (BK), 0.25 +/- 0.03 (AII), or 0.12 +/- 0.03 (Hem) fM/microg protein (p < 0.05). L-arginine methyl ester (100 microM) inhibited clofibrate-induced reduction in basal ET-1 production. Clofibrate increased PPARalpha expression, accompanied by increased NO production and eNOS expression. PKC inhibition by calphostin C (10 microM) blocked these effects, whereas activation by PMA reduced basal PPARalpha expression. Thus, PPARalpha activation attenuated ET-1 production by agents that mediate brain injury through mechanisms that probably result from PPARalpha-induced increase in eNOS expression/NO production and complex PKC signaling pathways. Therefore, PPARalpha activators can be appropriate therapeutic agents to alleviate cerebrovascular dysfunction following cerebral vasospasm.
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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.