2023
Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network
Clark J, Garvey W, Niswender K, Schmidt A, Ahima R, Aleman J, Battarbee A, Beckman J, Bennett W, Brown N, Chandler‐Laney P, Cox N, Goldberg I, Habegger K, Harper L, Hasty A, Hidalgo B, Kim S, Locher J, Luther J, Maruthur N, Miller E, Sevick M, Wells Q. Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network. Journal Of The American Heart Association 2023, 12: e027693. PMID: 36752232, PMCID: PMC10111504, DOI: 10.1161/jaha.122.027693.Peer-Reviewed Original ResearchConceptsAmerican Heart AssociationHeart AssociationWeight loss interventionNovel therapeutic approachesVanderbilt University Medical CenterUniversity Medical CenterEffective therapeutic interventionsField of obesityResearch NetworkLoss interventionClinical trialsWorldwide prevalenceMedical CenterTherapeutic approachesObesityTherapeutic targetAnimal modelsJohns Hopkins University SchoolTherapeutic interventionsIndividual centersNew targetsUniversity of AlabamaOverweightUniversity SchoolIntervention
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 contributorTissueTreatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids
Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension 2021, 77: 1323-1331. PMID: 33583202, PMCID: PMC8320355, DOI: 10.1161/hypertensionaha.120.14808.Peer-Reviewed Original Research
2018
The Vasculature in Prediabetes
Wasserman DH, Wang TJ, Brown NJ. The Vasculature in Prediabetes. Circulation Research 2018, 122: 1135-1150. PMID: 29650631, PMCID: PMC5901903, DOI: 10.1161/circresaha.118.311912.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme InhibitorsAnimalsBlood VesselsCardiovascular DiseasesCombined Modality TherapyDiabetes Mellitus, Type 2Diet, ReducingDisease ProgressionEndothelium, VascularExtracellular MatrixFatty Acids, NonesterifiedFibrinolysisGlucoseHumansHyperglycemiaHypoglycemic AgentsInflammationInsulin ResistanceLife StyleMetabolic SyndromeMiceMicrocirculationMicroRNAsMuscle, SkeletalObesityPrediabetic StateRiskWeight LossConceptsFrequency of prediabetesMainstay of treatmentPrevalence of obesityConcomitant obesityEndothelial dysfunctionExtracellular matrix remodelingDiabetes mellitusEndothelial functionRenal diseaseMetabolic derangementsFibrinolytic dysfunctionEndothelial vasodilatorsInsulin resistanceInsulin sensitivityCardiovascular diseaseDelivery of insulinSlow progressionPrediabetesWeight lossSkeletal muscleMatrix remodelingMellitusObesityDysfunctionDisease
2016
Epoxyeicosatrienoic 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 evidenceMitochondrial dysfunction and oxidative stress in patients with chronic kidney disease
Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ, Himmelfarb J, Ikizler TA, Brown NJ. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiological Reports 2016, 4: e12780. PMID: 27162261, PMCID: PMC4873632, DOI: 10.14814/phy2.12780.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseCKD stage 5Peripheral blood mononuclear cellsSeverity of CKDCKD stage 3Kidney diseaseOxidative stressF2-isoprostanesMtDNA copy numberMuscle biopsyMitochondrial volume densitySkeletal muscleDifferent CKD stagesMitochondrial dysfunctionBlood mononuclear cellsStage 3Stage 5Skeletal muscle biopsiesLower mtDNA copy numberMitochondrial DNA copy numberPlasma isofuransCKD stageMuscle dysfunctionMononuclear cellsFunction worsens
2013
Introduction
Brown NJ, Falck J. Introduction. Prostaglandins And Other Lipid Mediators 2013, 104: 1. PMID: 23809194, DOI: 10.1016/j.prostaglandins.2013.06.003.Peer-Reviewed Original ResearchContribution of aldosterone to cardiovascular and renal inflammation and fibrosis
Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nature Reviews Nephrology 2013, 9: 459-469. PMID: 23774812, PMCID: PMC3922409, DOI: 10.1038/nrneph.2013.110.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAnimalsAromatase InhibitorsCardiovascular SystemCytochrome P-450 CYP11B2Endothelial CellsFadrozoleFibrosisHumansImidazolesInflammationKidneyMacrophagesMineralocorticoid Receptor AntagonistsMyocardiumMyocytes, CardiacPyridinesReactive Oxygen SpeciesReceptors, MineralocorticoidSodium, Dietary
2012
Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury
Luther JM, Luo P, Wang Z, Cohen SE, Kim HS, Fogo AB, Brown NJ. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury. Kidney International 2012, 82: 643-651. PMID: 22622494, PMCID: PMC3434275, DOI: 10.1038/ki.2012.170.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAnimalsAortaBiomarkersBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalFibrosisGene Expression RegulationHeart DiseasesInflammationKidney DiseasesKidney GlomerulusMiceMice, 129 StrainMice, Inbred C57BLMineralocorticoid Receptor AntagonistsMyocardiumReceptors, MineralocorticoidRenin-Angiotensin SystemSodium Chloride, DietarySpironolactoneTime FactorsVascular DiseasesConceptsMineralocorticoid receptor antagonismAbsence of aldosteroneAldosterone deficiencyAngiotensin IIReceptor antagonismMineralocorticoid receptorKnockout miceAldosterone synthase knockout (AS(-/-)) miceMineralocorticoid receptor antagonist spironolactonePlasminogen activator inhibitor-1 mRNA expressionAldosterone synthase inhibitionMineralocorticoid receptor activationPrevents angiotensin IIAngiotensin II treatmentSynthase knockout miceBlood urea nitrogenWild-type miceWild-type littermatesMineralocorticoid antagonismAntagonist spironolactoneAortic remodelingRenal injuryEndogenous aldosteroneGlomerular hypertrophyGlomerular injuryLysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension
Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Chen Y, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension. American Journal Of Hypertension 2012, 25: 812-817. PMID: 22534796, PMCID: PMC3721725, DOI: 10.1038/ajh.2012.43.Peer-Reviewed Original ResearchConceptsMinor allele carriersSalt-sensitive hypertensionBlood pressureSingle nuclear polymorphismsAllele carriersHypertensive cohortDietary saltWT miceLiberal salt dietLiberal salt intakeSystolic blood pressureSerum aldosterone concentrationHeterozygote knockout miceTranslational research studiesRenovascular responsivenessAldosterone concentrationSalt dietDietary sodiumSalt intakeSystolic BPHuman studiesHypertensionKnockout miceClinical relevanceCaucasian cohort
2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular levelAldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonismThis is not Dr. Conn's aldosterone anymore.
Brown NJ. This is not Dr. Conn's aldosterone anymore. Transactions Of The American Clinical And Climatological Association 2011, 122: 229-43. PMID: 21686229, PMCID: PMC3116341.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsAnimalsBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalEnzyme InhibitorsFibrosisGene Expression RegulationHumansHyperaldosteronismInflammation MediatorsKidneyLigandsMiceMineralocorticoid Receptor AntagonistsMyocardiumRatsReceptors, MineralocorticoidSignal TransductionTime FactorsConceptsMR-independent pathwayPrevalence of hyperaldosteronismAngiotensin receptor blockersMineralocorticoid receptor antagonismSecretion of aldosteroneAldosterone-secreting adenomasPro-fibrotic effectsReceptor blockersResistant hypertensionSevere hypertensionAldosterone concentrationRenal injuryEndogenous aldosteroneACE inhibitorsCardiovascular remodelingAngiotensin IIReceptor antagonismHeart diseaseProfibrotic effectsAldosteroneBaseline valuesEnzyme inhibitorsPatientsPotassium homeostasisHypertension
2010
Review: Therapeutic potential of plasminogen activator inhibitor-1 inhibitors
Brown NJ. Review: Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Therapeutic Advances In Cardiovascular Disease 2010, 4: 315-324. PMID: 20660535, DOI: 10.1177/1753944710379126.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Plasminogen Activator Inhibitor-1 InhibitorsInitiation of diabetesPathogenesis of thrombosisPotential therapeutic strategyActivator inhibitor-1Major physiological inhibitorRenal injuryVascular remodelingPreclinical studiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic potentialInhibitor-1Physiological inhibitorMolecule inhibitorsCell migrationInhibitorsThrombosisDiabetesFibrosisPathogenesisFibrinolysisInjuryDiseaseAldosterone and inflammation
Gilbert KC, Brown NJ. Aldosterone and inflammation. Current Opinion In Endocrinology Diabetes And Obesity 2010, 17: 199-204. PMID: 20422780, PMCID: PMC4079531, DOI: 10.1097/med.0b013e3283391989.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptorAngiotensin subtype 1 receptorAldosterone-induced inflammationMineralocorticoid receptor activationVascular collagen depositionMineralocorticoid receptor antagonistsSubtype 1 receptorInflammatory cell infiltrationVascular smooth muscle cellsAldosterone synthase inhibitorsNuclear factor-kappaBSmooth muscle cellsCell-specific effectsInflammatory phenotypeReceptor antagonistTissue inflammationCell infiltrationTherapeutic roleCollagen depositionSynthase inhibitorAldosteroneFactor-kappaBInflammationReceptor activationMuscle cells
2009
Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt
Lea WB, Kwak ES, Luther JM, Fowler SM, Wang Z, Ma J, Fogo AB, Brown NJ. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney International 2009, 75: 936-944. PMID: 19225557, PMCID: PMC2770712, DOI: 10.1038/ki.2009.9.Peer-Reviewed Original ResearchConceptsAldosterone synthase inhibitionEnd-organ damageHigh salt intakeWeeks of treatmentPlasminogen activator inhibitor-1Angiotensin IISynthase inhibitionMRNA expressionSalt intakeInterstitial fibrosisGrowth factor-beta mRNA expressionAortic medial hypertrophyMineralocorticoid receptor blockadeMineralocorticoid receptor antagonismHigh-salt dietCardiac interstitial fibrosisKidneys of ratsPAI-1 mRNA expressionActivator inhibitor-1MRNA protein expressionAldosterone antagonismHypertensive responseRenal effectsUninephrectomized ratsMedial hypertrophy
2008
Salt in the Wound
Brown NJ. Salt in the Wound. Journal Of The American Society Of Nephrology 2008, 20: 5-6. PMID: 19118146, DOI: 10.1681/asn.2008111185.Peer-Reviewed Original ResearchEndogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta
Luther JM, Wang Z, Ma J, Makhanova N, Kim HS, Brown NJ. Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta. Endocrinology 2008, 150: 2229-2236. PMID: 19106220, PMCID: PMC2671907, DOI: 10.1210/en.2008-1296.Peer-Reviewed Original ResearchConceptsPpET-1 expressionAng IIPlasminogen activator inhibitor-1Profibrotic gene expressionEndogenous aldosteroneActivator inhibitor-1PAI-1MRNA expressionWT miceAngiotensin IITGF-beta mRNA expressionInhibitor-1Acute angiotensin IIBasal PAI-1Plasma renin activityAcute stimulatory effectPpET-1 mRNA expressionTGF-beta expressionTissue mRNA expressionPreproendothelin-1 expressionRenin activityAldosterone concentrationH infusionAldosteronePpET-1Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine
Edgerton DS, Cherrington AD, Neal DW, Scott M, Lautz M, Brown N, Petro J, Hobbs CH, Leach C, Del Parigi A, Strack TR. Inhaled Insulin Is Associated with Prolonged Enhancement of Glucose Disposal in Muscle and Liver in the Canine. Journal Of Pharmacology And Experimental Therapeutics 2008, 328: 970-975. PMID: 19098161, PMCID: PMC3202424, DOI: 10.1124/jpet.108.146985.Peer-Reviewed Original ResearchConceptsInhalation of insulinPlasma glucose levelsGlucose levelsDiabetic patientsGlucose disposalNet hepatic glucose uptakeGlucose uptakeArterial plasma glucose levelsHepatic sinusoidal insulinBasal plasma levelsNonhepatic glucose uptakeGlucose infusion rateHepatic glucose uptakeInhalation groupInsulin inhalationSubcutaneous insulinPeripheral veinPlasma levelsPortal veinPlasma insulin kineticsInsulin secretionInfusion rateInsulin actionGlucose utilizationInhalationAldosterone and Vascular Inflammation
Brown NJ. Aldosterone and Vascular Inflammation. Hypertension 2008, 51: 161-167. PMID: 18172061, DOI: 10.1161/hypertensionaha.107.095489.Peer-Reviewed Original Research