ArticleThe Journal of pharmacology and experimental therapeutics2010
20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Bioactive lipid mediators in polycystic kidney disease.Journal of lipid research · 2014Trial
- 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
- pNaKtide Inhibits Na/K-ATPase Signaling and Attenuates Obesity.Journal of clinical and medical sciences · 2023Article
- Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension.Journal of pharmaceutical analysis · 2022Review
- Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis.International journal of molecular sciences · 2022Review
- The CYP/20-HETE/GPR75 axis in hypertension.Advances in pharmacology (San Diego, Calif.) · 2022Review
- Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases.Frontiers in nutrition · 2022Review
- Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- The Role of Epidermal Growth Factor Receptor Family of Receptor Tyrosine Kinases in Mediating Diabetes-Induced Cardiovascular Complications.Frontiers in pharmacology · 2021Review
- The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases.Frontiers in pharmacology · 2021Review
- Elevated lipoxygenase and cytochrome P450 products predict progression of chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Article
- 20-HETE in the regulation of vascular and cardiac function.Pharmacology & therapeutics · 2018Review
- Neurovascular dysfunction in vascular dementia, Alzheimer's and atherosclerosis.BMC neuroscience · 2018Review
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017Review
- Heme-thiolate sulfenylation of human cytochrome P450 4A11 functions as a redox switch for catalytic inhibition.The Journal of biological chemistry · 2017Article
- 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (GCirculation research · 2017Article
- Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction.American journal of physiology. Heart and circulatory physiology · 2017Article
- Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging.American journal of physiology. Heart and circulatory physiology · 2017Review
- Role of vascular reactive oxygen species in regulating cytochrome P450-4A enzyme expression in Dahl salt-sensitive rats.Microcirculation (New York, N.Y. : 1994) · 2016Article
- Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia.Brain pathology (Zurich, Switzerland) · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial dysfunction and activation occur in the vasculature and are believed to contribute to the pathogenesis of cardiovascular diseases. We have shown that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a cytochrome P450 4A-derived eicosanoid that promotes vasoconstriction in the microcirculation, uncouples endothelial nitric-oxide synthase (eNOS) and reduces nitric oxide (NO) levels via the dissociation of the 90-kDa heat shock protein (HSP90) from eNOS. It also causes endothelial activation by stimulating nuclear factor-kappaB (NF-kappaB) and increasing levels of pro-inflammatory cytokines. In this study, we examined signaling mechanisms that may link 20-HETE-induced endothelial dysfunction and activation. Under conditions in which 20-HETE inhibited NO production, it also stimulated inhibitor of NF-kappaB (IkappaB) phosphorylation. Both effects were prevented by inhibition of tyrosine kinases and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). It is noteworthy that inhibitor of IkappaB kinase (IKK) activity negated the 20-HETE-mediated inhibition of NO production. Immunoprecipitation experiments revealed that treatment of ionophore-stimulated cells with 20-HETE brings about a decrease in HSP90-eNOS association and an increase in HSP90-IKKbeta association, suggesting that the activation by 20-HETE of NF-kappaB is linked to its action on eNOS. Furthermore, addition of inhibitors of tyrosine kinase MAPK and IKK restored the 20-HETE-mediated impairment of acetylcholine-induced relaxation in rat renal interlobar arteries. The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation.
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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.