2008
Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population
Schoenhard JA, Asselbergs FW, Poku KA, Stocki SA, Gordon S, Vaughan DE, Brown NJ, Moore JH, Williams SM. Male–female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Human Genetics 2008, 124: 479-488. PMID: 18953568, PMCID: PMC2770717, DOI: 10.1007/s00439-008-0573-x.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1PAI-1 levelsTissue-type plasminogen activatorRenin polymorphismPAI-1 4G/5G polymorphismRenin-angiotensin systemDiastolic blood pressurePopulation-based sampleActivator inhibitor-1Large-scale population-based samplePAI-1 expressionBlood pressureTotal cholesterolThromboembolic diseasePlasma levelsRisk factorsCardiovascular diseaseD polymorphismMetabolic parametersG polymorphismFibrinolytic systemGene polymorphismsThrombus formationCaucasian subjectsGhanaian population
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
2003
Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass
Pretorius M, Murphey LJ, McFarlane JA, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass. Circulation 2003, 108: 3079-3083. PMID: 14656921, DOI: 10.1161/01.cir.0000105765.54573.60.Peer-Reviewed Original ResearchConceptsPostoperative day 1PAI-1 antigenCardiopulmonary bypassACE inhibitorsPAI-1 expressionACEI groupACE inhibitionPlasminogen activator inhibitor-1 (PAI-1) concentrationsTPA activityTissue-type plasminogen activator antigenAngiotensin-converting enzyme inhibitionAcute graft thrombosisPreoperative ACE inhibitorsMorning of surgeryCoronary artery bypassVein graft occlusionPlasminogen activator antigenArterial blood samplesArtery bypassGraft thrombosisGraft occlusionFibrinolytic responseAngiotensin IIBlood samplesDay 1Tissue- 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
2002
The Renin-Angiotensin-Aldosterone System and Fibrinolysis in Progressive Renal Disease
Brown NJ, Vaughan DE, Fogo AB. The Renin-Angiotensin-Aldosterone System and Fibrinolysis in Progressive Renal Disease. Seminars In Nephrology 2002, 22: 399-406. PMID: 12224047, DOI: 10.1053/snep.2002.34725.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Renal diseaseAldosterone systemProgressive renal diseaseFinal common pathwayActivator inhibitor-1Extracellular matrix accumulationPAI-1 expressionInitiating injuryRenal failureRenin-AngiotensinInterstitial fibrosisClinical managementMajor physiologic inhibitorAnimal modelsProduction of plasminFibrosisMatrix accumulationPlasminogen activatorPhysiologic inhibitorInhibitor-1Common pathwayDiseaseInjuryRAASAldosterone 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
2001
Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen
Brown N, Murphey L, Srikuma N, Koschachuhanan N, Williams G, Vaughan D. Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen. Arteriosclerosis Thrombosis And Vascular Biology 2001, 21: 1071-1077. PMID: 11397722, DOI: 10.1161/01.atv.21.6.1071.Peer-Reviewed Original ResearchConceptsPAI-1 4G/5G genotypePAI-1 antigen concentrationsPAI-1 antigenHigh salt intakeLow salt intakeSalt intakeG genotypeAntigen concentrationThrombotic cardiovascular eventsPlasma renin activityPAI-1 expressionPAI-1 geneAldosterone systemCardiovascular eventsCardiovascular morbidityRenin activityPharmacological therapyEssential hypertensionSerum triglyceridesEffects of activationG polymorphismG homozygotesG groupAntigenIntake
2000
Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo
Brown N, Nakamura S, Ma L, Nakamura I, Donnert E, Freeman M, Vaughan D, Fogo A. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney International 2000, 58: 1219-1227. PMID: 10972684, DOI: 10.1046/j.1523-1755.2000.00277.x.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAnimalsBlood PressureBlotting, NorthernCreatinineDisease ProgressionFibrosisGene ExpressionGlomerulosclerosis, Focal SegmentalIn Situ HybridizationKidney GlomerulusMaleMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1ProteinuriaRatsRats, Sprague-DawleyRNA, MessengerSpironolactoneConceptsPlasminogen activator inhibitor-1PAI-1 expressionBlood pressurePAI-1 mRNA expressionActivator inhibitor-1Development of sclerosisAldosterone antagonismMRNA expressionMale Sprague-Dawley ratsInhibitor-1Aldosterone antagonist spironolactoneDegree of sclerosisSprague-Dawley ratsMajor physiological inhibitorAldosterone systemAntagonist spironolactoneRenal injuryFibrinolytic balanceSignificant proteinuriaCombination therapySingle doseRadiation injuryRat modelAT1RAAldosteroneSynergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production1
Brown N, Kim K, Chen Y, Blevins L, Nadeau J, Meranze S, Vaughan D. Synergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production1. The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 336-344. PMID: 10634408, DOI: 10.1210/jcem.85.1.6305.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAdrenal GlandsAldosteroneAngiotensin IIAnimalsBlotting, NorthernCells, CulturedChromosome MappingDexamethasoneGenes, ReporterHumansHydrocortisoneHyperaldosteronismMuscle, Smooth, VascularMutagenesis, Site-DirectedPlasminogen Activator Inhibitor 1RatsTissue Plasminogen ActivatorTransfectionConceptsPAI-1 expressionAng IIEffects of aldosteroneAngiotensin IIVenous bloodTissue plasminogen activator antigenPAI-1 antigen concentrationsSelective adrenal veinHuman PAI-1 promoterL Ang IIPeripheral venous bloodRat aortic smooth muscle cellsAdrenal venous bloodPlasminogen activator antigenAortic smooth muscle cellsPlasminogen activator inhibitor-1 productionCultured human umbilical vein endothelial cellsPlasminogen activator inhibitor expressionPAI-1 antigenSmooth muscle cellsHuman umbilical vein endothelial cellsDose-dependent mannerUmbilical vein endothelial cellsL aldosteroneAdrenal vein