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 injury
2011
Epistatic Interactions in Genetic Regulation of t-PA and PAI-1 Levels in a Ghanaian Population
Penrod NM, Poku KA, Vaughn D, Asselbergs FW, Brown NJ, Moore JH, Williams SM. Epistatic Interactions in Genetic Regulation of t-PA and PAI-1 Levels in a Ghanaian Population. PLOS ONE 2011, 6: e16639. PMID: 21304999, PMCID: PMC3031598, DOI: 10.1371/journal.pone.0016639.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceEpistasis, GeneticFemaleGene Expression RegulationGhanaHumansMalePlasminogen Activator Inhibitor 1Polymorphism, GeneticSex FactorsTissue Plasminogen ActivatorConceptsEpistatic interactionsPAI-1 levelsRenin-angiotensin systemMultiple genetic effectsPathway-specific genesD polymorphismPAI-1Genetic architectureT-PASingle SNP analysisGenetic regulationCentral genesSpecific genesCardiovascular diseaseFibrinolytic systemSNP analysisGenetic effectsGenesCleavage of angiotensinogenPlasminogen activator inhibitor-1Plasma t-PAT-PA levelsTissue plasminogen activatorActivator inhibitor-1Enzyme cleavageThis 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
2007
Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency
Brown NJ, Bradford J, Wang Z, Lea W, Ma L, Ma J, Vaughan DE, Fogo AB. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney International 2007, 72: 72-81. PMID: 17429342, DOI: 10.1038/sj.ki.5002268.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsAortaBlood PressureGene Expression RegulationKidneyLiverLosartanMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNorepinephrinePlasminogen Activator Inhibitor 1Random AllocationReceptor, Angiotensin, Type 1RNA, MessengerVasoconstrictor AgentsConceptsPAI-1 expressionPlasminogen activator inhibitor-1 expressionSystolic blood pressureAng IIBlood pressureReceptor deficiencyWT miceAngiotensin IIBaseline systolic blood pressureAT1a receptor deficiencyEffects of losartanReceptor knockout micePressor responseWT heartsReceptor mRNAKnockout miceLosartanNorepinephrinePAI-1AortaKidneyLiverMiceCell-type specificHeart
2004
Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling
Weisberg AD, Albornoz F, Griffin JP, Crandall DL, Elokdah H, Fogo AB, Vaughan DE, Brown NJ. Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2004, 25: 365-371. PMID: 15576638, DOI: 10.1161/01.atv.0000152356.85791.52.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAdministration, OralAngiotensin IIAnimalsAntigens, DifferentiationAortaAortic DiseasesBlood PressureChemokine CCL2Collagen Type ICollagen Type IIIDrug Evaluation, PreclinicalFibronectinsFibrosisGene Expression RegulationGlomerulosclerosis, Focal SegmentalHeartHypertrophy, Left VentricularIndoleacetic AcidsIndolesKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1Random AllocationRNA, MessengerSialoglycoproteinsSingle-Blind MethodSodium Chloride, DietaryConceptsAng IIAortic remodelingCardiac fibrosisPAI-039PAI-1 inhibitionVascular remodelingCardiac hypertrophyMouse modelHeart/body weight ratioAng II/saltWall thickeningPharmacological inhibitionSmall molecule PAI-1 inhibitorAortic mRNA expressionHigh salt intakeAortic wall thickeningMale C57BL/6J miceBody weight ratioChemoattractant protein-1PAI-1 deficiencyPAI-1 activityPAI-1 inhibitorPlasminogen activator inhibitorPressor responseAngiotensin IIAn application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation
Coffey CS, Hebert PR, Ritchie MD, Krumholz HM, Gaziano JM, Ridker PM, Brown NJ, Vaughan DE, Moore JH. An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation. BMC Bioinformatics 2004, 5: 49. PMID: 15119966, PMCID: PMC419697, DOI: 10.1186/1471-2105-5-49.Peer-Reviewed Original ResearchGene Expression RegulationGenetic Predisposition to DiseaseGenotypeHumansLogistic ModelsMyocardial InfarctionRisk Assessment
2003
Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice
Eren M, Painter CA, Gleaves LA, Schoenhard JA, Atkinson JB, Brown NJ, Vaughan DE. Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice. Journal Of Thrombosis And Haemostasis 2003, 1: 2389-2396. PMID: 14629474, DOI: 10.1046/j.1538-7836.2003.00437.x.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsGene Expression RegulationGreen Fluorescent ProteinsHumansImmunohistochemistryLipopolysaccharidesLuminescent ProteinsMiceMice, TransgenicOrgan SpecificityPlasminogen Activator Inhibitor 1Promoter Regions, GeneticTissue DistributionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsTranscriptional responseMurine PAI-1Plasminogen activator inhibitor-1 promoterPhysiological regulationPAI-1 promoterPlasminogen activator inhibitor type 1 (PAI-1) expressionGreen fluorescent proteinAgonist-specific regulationTranscription factorsTransgenic strategiesTransgenic miceDNA sequencesPAI-1 expressionHeterologous promoterAng IIQuantitative regulationRegulatory mechanismsRegulatory factorsFluorescent proteinKb promoterTransgenic animalsPhysiological relevancePromoterFunctional studiesEGFP expression