2021
The soluble epoxide hydrolase inhibitor GSK2256294 decreases the proportion of adipose pro-inflammatory T cells
Mashayekhi M, Wanjalla CN, Warren CM, Simmons JD, Ghoshal K, Pilkinton M, Bailin SS, Gabriel CL, Pozzi A, Koethe JR, Brown NJ, Kalams SA, Luther JM. The soluble epoxide hydrolase inhibitor GSK2256294 decreases the proportion of adipose pro-inflammatory T cells. Prostaglandins And Other Lipid Mediators 2021, 158: 106604. PMID: 34922004, PMCID: PMC8742790, DOI: 10.1016/j.prostaglandins.2021.106604.Peer-Reviewed Original ResearchConceptsPro-inflammatory T cellsEpoxyeicosatrienoic acidsSoluble epoxide hydrolaseSystemic inflammationT cellsAdipose tissueSubcutaneous abdominal adipose tissueEnzyme soluble epoxide hydrolaseComplex immune environmentT cell profileAbdominal adipose tissuePrediabetic adultsImmune environmentObese individualsSEH inhibitionObese personsTumor necrosisObese animalsInflammationCrossover designCell profilesGSK2256294Epoxide hydrolaseCentral contributorTissue
2017
Two Pools of Epoxyeicosatrienoic Acids in Humans
Elijovich F, Milne GL, Brown NJ, Laniado-Schwartzman M, Laffer CL. Two Pools of Epoxyeicosatrienoic Acids in Humans. Hypertension 2017, 71: 346-355. PMID: 29279315, PMCID: PMC5764817, DOI: 10.1161/hypertensionaha.117.10392.Peer-Reviewed Original ResearchConceptsSalt-resistant subjectsDihydroxyeicosatrienoic acidsEpoxyeicosatrienoic acidsBlood pressurePlasma epoxyeicosatrienoic acidsRegulation of natriuresisSalt-sensitive subjectsUrine sodium excretionPotential therapeutic implicationsRenal poolSodium excretionInpatient protocolNormotensive subjectsFractional excretionVascular dysfunctionVascular toneSystemic originTherapeutic implicationsTotal poolNatriuresisSalt loadingExcretionUrine poolsAldosteroneCatecholamines
2016
Abstract P189: Disruption of Cyp2c44 Increases Sodium Chloride Cotransporter Expression and Activity in the Distal Convoluted Tubule
Su X, Wang L, Gao Z, Lin D, Pandey V, Wang T, Abraham N, Schwartzman M, Wang W. Abstract P189: Disruption of Cyp2c44 Increases Sodium Chloride Cotransporter Expression and Activity in the Distal Convoluted Tubule. Hypertension 2016, 68 DOI: 10.1161/hyp.68.suppl_1.p189.Peer-Reviewed Original ResearchNaCl cotransporterNCC expressionEpoxyeicosatrienoic acidsENaC activityRegulation of renal sodium transportFat diet-induced increaseIncreased ENaC activityAlanine-rich kinaseEffect of hydrochlorothiazideRenal sodium transportDietary Na intakeDistal convoluted tubuleCytochrome-P450Cotransporter expressionWT miceRenal expressionNCC activityKO miceNa intakeNa excretionCyp2c44Sodium transportNa transportNa absorptionENaCEpoxyeicosatrienoic acids and glucose homeostasis in mice and men
Luther JM, Brown NJ. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men. Prostaglandins And Other Lipid Mediators 2016, 125: 2-7. PMID: 27448715, PMCID: PMC5035218, DOI: 10.1016/j.prostaglandins.2016.07.010.Peer-Reviewed Original ResearchConceptsEpoxyeicosatrienoic acidsInsulin sensitivityRodent modelsSoluble epoxide hydrolaseGlucose homeostasisEpoxide hydrolaseActive dihydroxyeicosatrienoic acidsPancreatic islet cell functionEffects of EETsType 2 diabetesType 1 diabetesIslet cell functionP450 epoxygenasesDihydroxyeicosatrienoic acidsPeripheral tissuesIslet cellsPharmacological inhibitionArachidonic acidDiabetesCell functionGenetic polymorphismsFavorable effectTissue expressionStable analogueCompelling evidence
2014
Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans
Ramirez CE, Shuey MM, Milne GL, Gilbert K, Hui N, Yu C, Luther JM, Brown NJ. Arg287Gln variant of EPHX2 and epoxyeicosatrienoic acids are associated with insulin sensitivity in humans. Prostaglandins And Other Lipid Mediators 2014, 113: 38-44. PMID: 25173047, PMCID: PMC4253976, DOI: 10.1016/j.prostaglandins.2014.08.001.Peer-Reviewed Original ResearchConceptsInsulin sensitivity indexEpoxyeicosatrienoic acidsInsulin sensitivityHigher insulin sensitivity indexPlasma epoxyeicosatrienoic acidsGlucose-stimulated insulin secretionBody mass indexArg/ArgSoluble epoxide hydrolase activitySoluble epoxide hydrolaseMetabolic syndromeMass indexDisposition indexInsulin resistanceHyperglycemic clampInsulin secretionSensitivity indexEpoxide hydrolase activityEPHX2Hydrolase activitySecretionPhenotyping studiesMetabolic phenotyping studiesEpoxide hydrolaseGenetic variants
2011
CYP4A11 variant is associated with high-density lipoprotein cholesterol in women
White CC, Feng Q, Cupples LA, Gainer JV, Dawson EP, Wilke RA, Brown NJ. CYP4A11 variant is associated with high-density lipoprotein cholesterol in women. The Pharmacogenomics Journal 2011, 13: 44-51. PMID: 21912424, PMCID: PMC3380161, DOI: 10.1038/tpj.2011.40.Peer-Reviewed Original ResearchConceptsHigh-density lipoprotein cholesterolFramingham Offspring StudyEpoxyeicosatrienoic acidsLipoprotein cholesterolLow HDLOffspring StudyHDL-C concentrationsCYP4A11 variantsMetabolic parametersPPARα activationEndogenous peroxisomeHDLBioVU cohortWomenReduced activityΩ-hydroxylaseCohortCYP4A11CholesterolPrevalenceGenotypes
2010
Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans
Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans. Hypertension 2010, 57: 116-122. PMID: 21098312, PMCID: PMC3020911, DOI: 10.1161/hypertensionaha.110.161695.Peer-Reviewed Original ResearchConceptsForearm blood flowVariant allele carriersForearm vasodilator responseForearm vascular resistanceSoluble epoxide hydrolaseVascular resistanceVasodilator responseBlood flowAllele carriersSodium nitroprussideVascular functionStrain-gauge venous occlusion plethysmographyHighest forearm blood flowLower forearm vascular resistanceSignificant associationCytochrome P450-derived epoxyeicosatrienoic acidsEpoxide hydrolaseVenous occlusion plethysmographyCardiovascular disease riskEndothelium-independent mannerWild-type individualsOcclusion plethysmographyPotent vasodilatorEpoxyeicosatrienoic acidsPreclinical models
2007
Acute tissue-type plasminogen activator release in human microvascular endothelial cells: The roles of Gαq, PLC-β, IP3 and 5,6-epoxyeicosatrienoic acid
Muldowney JA, Painter CA, Sanders-Bush E, Brown NJ, Vaughan DE. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: The roles of Gαq, PLC-β, IP3 and 5,6-epoxyeicosatrienoic acid. Thrombosis And Haemostasis 2007, 97: 263-271. PMID: 17264956, DOI: 10.1160/th05-02-0092.Peer-Reviewed Original ResearchMeSH Keywords8,11,14-Eicosatrienoic AcidAortaBiological FactorsCell ProliferationCells, CulturedDose-Response Relationship, DrugEndothelial CellsEpoprostenolGTP-Binding Protein alpha Subunits, Gq-G11HumansInositol 1,4,5-TrisphosphateIsoenzymesMicrocirculationNitric OxidePhospholipase C betaPotassiumSignal TransductionThrombinTime FactorsTissue Plasminogen ActivatorType C PhospholipasesUmbilical VeinsConceptsT-PA releaseHuman microvascular endothelial cellsMicrovascular endothelial cellsEpoxyeicosatrienoic acidsTissue-type plasminogen activatorTissue-type plasminogen activator releaseEndothelial cellsIP3 receptor antagonistCalcium signalingT-PA antigenRole of GαqPlasminogen activator releaseMS-PPOHPhysiologic releaseCytochrome P450 inhibitorsL-NAMEEET antagonistReceptor antagonistActivator releaseVascular homeostasisNitric oxideProstacyclinPlasminogen activatorEET-methyl esterMicroM concentration
2006
Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC
Sun P, Lin D, Wang T, Babilonia E, Wang Z, Jin Y, Kemp R, Nasjletti A, Wang W. Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC. American Journal Of Physiology. Renal Physiology 2006, 291: f1192-f1200. PMID: 16849695, DOI: 10.1152/ajprenal.00112.2006.Peer-Reviewed Original ResearchMeSH Keywords8,11,14-Eicosatrienoic AcidAnimalsArachidonic AcidCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemEpithelial Sodium ChannelsFemaleIon Channel GatingKidney Tubules, CollectingMaleMembrane PotentialsPatch-Clamp TechniquesRatsRats, Sprague-DawleySodium, DietarySpecific Pathogen-Free OrganismsConceptsExpression of CYP2C23Low Na intakeCollecting ductsMS-PPOHEpoxyeicosatrienoic acidsDistal nephronArachidonic acidNa intakeInhibition of CYP epoxygenaseNa transportNa absorptionArachidonic acid-induced inhibitionControl Na dietInhibition of ENaC.Na-deficient dietNormal-Na dietActivation of ENaCEpithelial Na channelPatch-clamp studiesHigh-Na dietIncreased Na absorptionAA-induced inhibitionInhibitory effectENaC activityNa restriction
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