2012
Obesity and Oxidative Stress Predict AKI after Cardiac Surgery
Billings FT, Pretorius M, Schildcrout JS, Mercaldo ND, Byrne JG, Ikizler TA, Brown NJ. Obesity and Oxidative Stress Predict AKI after Cardiac Surgery. Journal Of The American Society Of Nephrology 2012, 23: 1221-1228. PMID: 22626819, PMCID: PMC3380645, DOI: 10.1681/asn.2011090940.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAngiotensin-Converting Enzyme InhibitorsBiomarkersBody Mass IndexCardiac Surgical ProceduresDiureticsF2-IsoprostanesFemaleHumansInterleukin-6MaleMiddle AgedObesityOxidative StressPlasminogen Activator Inhibitor 1Postoperative ComplicationsRamiprilRandomized Controlled Trials as TopicRisk FactorsSignal TransductionSpironolactone
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 ResearchConceptsEpistatic 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 cleavage
2008
Endogenous 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-1
2007
Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass
Pretorius M, Donahue BS, Yu C, Greelish JP, Roden DM, Brown NJ. Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass. Circulation 2007, 116: i-1-i-7. PMID: 17846288, DOI: 10.1161/circulationaha.106.677906.Peer-Reviewed Original ResearchConceptsPostoperative atrial fibrillationPAI-1 antigen concentrationsCardiopulmonary bypassAtrial fibrillationPlasminogen activator inhibitor-1Remote historyIndependent predictorsActivator inhibitor-1Antigen concentrationPAI-1Development of AFRisk of AFInhibitor-1Administration of protaminePreoperative PAI-1Elective cardiac surgeryTime of surgeryPAI-1 concentrationsBlood of patientsHospital stayValve surgeryAdult patientsYounger patientsCardiac surgerySignificant morbidityModulation 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
2005
Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia
Ma J, Albornoz F, Yu C, Byrne DW, Vaughan DE, Brown NJ. Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia. Hypertension 2005, 46: 326-332. PMID: 15998706, DOI: 10.1161/01.hyp.0000174327.53863.86.Peer-Reviewed Original ResearchMeSH KeywordsAdultCross-Over StudiesDiureticsDouble-Blind MethodElectrolytesFemaleFibrinolysisHemodynamicsHumansHydrochlorothiazideHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1PotassiumReceptors, MineralocorticoidRenin-Angiotensin SystemSodium Chloride Symporter InhibitorsSpironolactoneTriamtereneConceptsPAI-1 antigenMineralocorticoid receptor antagonismHypertensive subjectsPAI-1 responseTissue-type plasminogen activatorAldosterone systemNormotensive subjectsFibrinolytic balanceReceptor antagonismMelanocortin 4 receptor-deficient micePlasminogen activator inhibitor-1 (PAI-1) concentrationsEffect of spironolactoneReceptor-deficient miceEffect of triamtereneBlood pressureSerum potassiumTreatment groupsEffects of activationSpironolactonePAI-1Plasminogen activatorAntigenTriamtereneRegression analysisSubjects
2004
Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1
Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1. Diabetes 2004, 53: 336-346. PMID: 14747283, DOI: 10.2337/diabetes.53.2.336.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAnimalsBlood GlucoseCalorimetry, IndirectCarrier ProteinsDisease Models, AnimalGlucose Clamp TechniqueHyperinsulinismInsulinInsulin ResistanceIntercellular Signaling Peptides and ProteinsIon ChannelsMaleMembrane ProteinsMiceMice, KnockoutMitochondrial ProteinsObesityPlasminogen Activator Inhibitor 1Polymerase Chain ReactionProteinsRNA, MessengerTranscription, GeneticTriglyceridesUncoupling Protein 1Weight GainConceptsPlasminogen activator inhibitor-1Prevention of obesityInsulin resistanceHF dietWT miceActivator inhibitor-1Insulin sensitivityPAI-1Angiotensin type 1 receptor antagonistType 1 receptor antagonistDiet-induced obesity modelEuglycemic hyperinsulinemic clamp studyProtein-3 mRNA expressionInhibitor-1PAI-1-deficient micePeroxisome proliferator-activated receptorDiet-induced obesityPAI-1 levelsPAI-1 deficiencyPAI-1 increaseWhite adipose tissueProliferator-activated receptorInsulin-stimulated glucose uptakeTotal energy expenditureDirect causal role
2003
Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1
Sawathiparnich P, Murphey LJ, Kumar S, Vaughan DE, Brown NJ. Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 3867-3873. PMID: 12915681, DOI: 10.1210/jc.2003-030374.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsBenzimidazolesBiphenyl CompoundsDiureticsElectrolytesFemaleFibrinolysisFurosemideHemodynamicsHumansMaleMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1Potassium ChlorideReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSingle-Blind MethodSpironolactoneTetrazolesConceptsMean arterial pressureAldosterone receptor antagonismAng IIReceptor antagonismPAI-1Angiotensin II type 1Coadministration of spironolactoneEffects of candesartanFurosemide-induced increasePresence of candesartanAldosterone receptor antagonistsEndogenous Ang IIPlasminogen activator inhibitor-1PAI-1 antigenActivator inhibitor-1PAI-1 productionPlasminogen activator inhibitorAldosterone systemNormotensive subjectsArterial pressureAngiotensin IIAT1 receptorFibrinolytic variablesReceptor antagonistCandesartan
2002
Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans
Sawathiparnich P, Kumar S, Vaughan DE, Brown NJ. Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 448-452. PMID: 11836266, DOI: 10.1210/jcem.87.2.7980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAldosteroneAntihypertensive AgentsBlood PressureCross-Over StudiesDiureticsDouble-Blind MethodFibrinolysisHumansHydrochlorothiazideHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1Sodium Chloride Symporter InhibitorsSpironolactoneConceptsPAI-1 antigenT-PA antigenAngiotensin IITissue-type plasminogen activator antigenEffect of spironolactoneSystolic blood pressureMale hypertensive subjectsPlasminogen activator antigenPlasminogen activator inhibitor-1Plasminogen activator inhibitor-1 productionActivator inhibitor-1PAI-1 productionAldosterone systemHypertensive subjectsSerum aldosteroneBlood pressureEndogenous aldosteroneHemodynamic parametersAldosteroneStudy daysSpironolactoneHCTZPAI-1AntigenInhibitor-1Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women
Brown NJ, Abbas A, Byrne D, Schoenhard JA, Vaughan DE. Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women. Circulation 2002, 105: 304-309. PMID: 11804984, DOI: 10.1161/hc0302.102570.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBlood PressureCardiovascular DiseasesCross-Over StudiesDrug Therapy, CombinationEstradiolEstrogen Replacement TherapyEstrogens, Conjugated (USP)FemaleHumansMiddle AgedPlasminogen Activator Inhibitor 1Polymorphism, GeneticPostmenopauseRamiprilReninSingle-Blind MethodTissue Plasminogen ActivatorConceptsHealthy postmenopausal womenPAI-1 4G/5G genotypePlasma renin activityPostmenopausal womenPAI-1 concentrationsACE inhibitionTissue plasminogen activatorConjugated estrogensPAI-1G genotypeRenin activityAngiotensin IIPlasminogen activator inhibitor-1 (PAI-1) concentrationsAngiotensin-Converting Enzyme InhibitionPAI-1 antigen concentrationsPlasminogen activatorConjugated equine estrogensEffects of estrogenPlasminogen activator inhibitor-1Activator inhibitor-1Combination estrogenClinical outcomesEquine estrogensCombined therapyCrossover treatmentAldosterone and PAI-1: implications for renal injury.
Brown NJ, Vaughan DE, Fogo AB. Aldosterone and PAI-1: implications for renal injury. Journal Of Nephrology 2002, 15: 230-5. PMID: 12113592.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Activator inhibitor-1Renal injuryAnimal modelsInhibitor-1Aldosterone receptor antagonismPlasminogen activator inhibitor-1 expressionExtracellular matrix accumulationPAI-1 expressionMajor physiological inhibitorRenal diseaseAngiotensin IIReceptor antagonismClinical managementAldosteroneProduction of plasminPAI-1FibrosisMatrix accumulationPlasminogen activatorInjuryPhysiological inhibitorVivoExpressionDisease
1999
Role of Angiotensin II in Coagulation and Fibrinolysis
Brown N, Vaughan D. Role of Angiotensin II in Coagulation and Fibrinolysis. Heart Failure Reviews 1999, 3: 193-198. DOI: 10.1023/a:1009757416302.Peer-Reviewed Original ResearchAntithrombotic effectAngiotensin type 1 receptor antagonistType 1 receptor antagonistVascular fibrinolytic balanceRenin-angiotensin systemTissue plasminogen activatorHypertensive patientsInhibitor PAI-1Angiotensin IIFibrinolytic balanceReceptor antagonistVasculoprotective propertiesPlatelet functionEnzyme inhibitorsPAI-1Plasminogen activatorMultiple mechanismsFibrinolysisSubstantial evidenceRecent studiesAngiotensinPatientsProstanoidsAntagonist
1998
Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1
Brown N, Agirbasli M, Williams G, Litchfield W, Vaughan D. Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1. Hypertension 1998, 32: 965-971. PMID: 9856958, DOI: 10.1161/01.hyp.32.6.965.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsCatecholaminesCircadian RhythmCreatinineDiet, Sodium-RestrictedFibrinolysisHemodynamicsHumansHydrocortisoneIsoquinolinesMalePlasminogen Activator Inhibitor 1QuinaprilReninRenin-Angiotensin SystemSodiumSupine PositionTetrahydroisoquinolinesTissue Plasminogen ActivatorConceptsLow salt intakeRenin-angiotensin systemPAI-1 antigenPlasma renin activitySalt intakeACE inhibitionMyocardial infarctionTPA antigenFibrinolytic systemPAI-1Plasminogen activator inhibitor-1 activityTissue-type plasminogen activator antigenPAI-1 antigen concentrationsPAI-1 antigen levelsThrombotic cardiovascular eventsHigh salt intakeLeft ventricular dysfunctionRecurrent myocardial infarctionPlasminogen activator antigenInhibitor-1 activityPlasma PAI-1PAI-1 activityConcomitant ACE inhibitionCardiovascular eventsRenin activityRegulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature
Stein C, Brown N, Vaughan D, Lang C, Wood A. Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature. Journal Of The American College Of Cardiology 1998, 32: 117-122. PMID: 9669258, DOI: 10.1016/s0735-1097(98)00210-1.Peer-Reviewed Original ResearchConceptsT-PA releaseTissue-type plasminogen activator releaseAdministration of isoproterenolSodium nitroprussidePlasminogen activator releaseVascular endotheliumActivator releasePAI-1Local t-PA releaseAdministration of SNPT-PA antigen levelsNet t-PA releasePlasma t-PA levelsEndothelium-independent agonistsForearm plasma flowNitric oxide agonistsForearm blood flowBeta-adrenoceptor agonistsVenous blood samplesRisk of thrombosisT-PA levelsEnzyme-linked immunosorbent assayPlasminogen activator inhibitorNormotensive menBrachial artery
1997
Plasminogen actiwator inhibitor type 1 in diabetes and hypertension
Litchfield W, Brown N, Vaughan D. Plasminogen actiwator inhibitor type 1 in diabetes and hypertension. Current Opinion In Endocrinology Diabetes And Obesity 1997, 4: 233-238. DOI: 10.1097/00060793-199706000-00009.Peer-Reviewed Original ResearchCardiovascular riskPAI-1Inhibitor type 1Type 1Elevated levelsIncreased cardiovascular riskRenin-angiotensin systemEndogenous fibrinolytic systemPlasminogen activator inhibitor type 1Activator inhibitor type 1Tissue plasminogen activatorHypertensive patientsEssential hypertensionMyocardial infarctionCardiovascular diseaseFibrinolytic systemHypertensionPlasminogen activatorStrong associationIncidenceRiskPrimary inhibitorHyperinsulinemiaHypertriglyceridemiaInfarctionSelective Stimulation of Tissue-Type Plasminogen Activator (t-PA) In Vivo by Infusion of Bradykinin
Brown N, Nadeau J, Vaughan D. Selective Stimulation of Tissue-Type Plasminogen Activator (t-PA) In Vivo by Infusion of Bradykinin. Thrombosis And Haemostasis 1997, 77: 522-525. PMID: 9066005, DOI: 10.1055/s-0038-1656000.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood PressureBradykininCaptoprilFemaleHumansHypertensionIsoquinolinesMalePlasminogen Activator Inhibitor 1QuinaprilRandomized Controlled Trials as TopicTetrahydroisoquinolinesTissue Plasminogen ActivatorConceptsT-PA antigen levelsTissue-type plasminogen activatorMean arterial pressureT-PA levelsAntigen levelsPAI-1 antigen levelsInfusion of bradykininSympathetic nervous systemEffect of bradykininTissue-type plasminogen activator secretionHypertensive patientsHemodynamic effectsArterial pressurePlasminogen activator secretionAngiotensin IIAnimal modelsPotent stimulusNervous systemPAI-1ACEIBradykininBradykinin resultsSelective stimulationPlasminogen activatorSignificant decrease
1996
The Renin-Angiotensin and Fibrinolytic Systems Co-Conspirators in the Pathogenesis of Ischemic Cardiovascular Disease
Brown N, Vaughan D. The Renin-Angiotensin and Fibrinolytic Systems Co-Conspirators in the Pathogenesis of Ischemic Cardiovascular Disease. Trends In Cardiovascular Medicine 1996, 6: 239-243. PMID: 21232303, DOI: 10.1016/s1050-1738(96)00091-6.Peer-Reviewed Original ResearchTissue-type plasminogen activatorFibrinolytic systemIschemic cardiovascular eventsRenin-angiotensin systemBreakdown of bradykininCardiovascular eventsAngiotensin IIT-PA secretionClinical observationsPotent stimulusStimulates releaseAngiotensin IPAI-1Plasminogen activatorVivo dataMajor inhibitorACEAngiotensinBradykininSecretionVasculature