2022
Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial
Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obesity And Metabolism 2022, 25: 570-580. PMID: 36306151, PMCID: PMC10306232, DOI: 10.1111/dom.14903.Peer-Reviewed Original ResearchConceptsFlow-mediated vasodilationPlasminogen activator inhibitor-1Vascular endothelial functionEndothelial functionInsulin resistanceWeight lossGlucagon-like peptide-1 receptor agonistsBaseline flow-mediated vasodilationDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent mechanismsPeptide-1 receptor agonistsBeneficial effectsEndothelial vasodilator functionGreater endothelial dysfunctionIncretin-based therapiesNormal endothelial functionChemoattractant protein-1Chemokine MCP-1Significant weight lossActivator inhibitor-1Effect of treatmentVasodilator functionUrine albuminEndothelial dysfunction
2017
Genetic Effects on the Correlation Structure of CVD Risk Factors Exome-Wide Data From a Ghanaian Population
Kodaman N, Sobota RS, Asselbergs FW, Oetjens MT, Moore JH, Brown NJ, Aldrich MC, Williams SM. Genetic Effects on the Correlation Structure of CVD Risk Factors Exome-Wide Data From a Ghanaian Population. Global Heart 2017, 12: 133-140. PMID: 28408189, PMCID: PMC5642993, DOI: 10.1016/j.gheart.2017.01.013.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1CVD risk factorsRisk factorsCardiovascular disease risk factorsDisease risk factorsHigh blood pressureActivator inhibitor-1Dissolution of thrombusArterial pressureBlood pressureMyocardial infarctionPlasma concentrationsStudy participantsGhanaian populationInhibitor-1Significant heterogeneityHeterogeneity of correlationAfrican AmericansGenetic variantsGenetic association studiesDirect role
2016
Plasminogen Activator Inhibitor‐1 and Diagnosis of the Metabolic Syndrome in a West African Population
Kodaman N, Aldrich MC, Sobota R, Asselbergs FW, Brown NJ, Moore JH, Williams SM. Plasminogen Activator Inhibitor‐1 and Diagnosis of the Metabolic Syndrome in a West African Population. Journal Of The American Heart Association 2016, 5: e003867. PMID: 27697752, PMCID: PMC5121488, DOI: 10.1161/jaha.116.003867.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntihypertensive AgentsBlood GlucoseBlood PressureBody Mass IndexCholesterol, HDLCross-Sectional StudiesDiabetes MellitusFastingFemaleGhanaHumansHypertensionHypoglycemic AgentsMaleMetabolic SyndromeMiddle AgedPlasminogen Activator Inhibitor 1PrevalenceRural PopulationTriglyceridesUrban PopulationYoung AdultConceptsPlasminogen activator inhibitor-1Activator inhibitor-1Metabolic syndromeRisk factorsDiagnostic criteriaLow high-density lipoproteinInhibitor-1Relevance of MetSAge-standardized prevalenceConventional risk factorsCardiovascular disease riskBody mass indexMetS diagnostic criteriaPAI-1 levelsHigh-density lipoproteinCross-sectional analysisMetS prevalenceIschemic eventsMetS componentsMetS criteriaWest African populationsMass indexPlasma levelsGhanaian menAntifibrinolytic factors
2015
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial
Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 4533-4540. PMID: 26580240, PMCID: PMC4667163, DOI: 10.1210/jc.2015-3415.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlbuminuriaDouble-Blind MethodEndothelium, VascularFemaleFibrinolysisGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHemodynamicsHumansInsulinInsulin ResistanceMaleMiddle AgedOverweightPhosphodiesterase 5 InhibitorsPlasminogen Activator Inhibitor 1Prediabetic StateSildenafil CitrateConceptsPhosphodiesterase-5 inhibitionGlucose-stimulated insulin secretionInsulin sensitivity indexInsulin sensitivityInsulin secretionBaseline insulin sensitivity indexPlacebo-controlled studyClinical Research CenterBody mass indexEnd of treatmentPlasminogen activator inhibitor-1Tissue plasminogen activatorActivator inhibitor-1Placebo groupUrine albuminSildenafil groupCreatinine ratioEndothelial functionPrimary outcomeMass indexTreatment armsFibrinolytic balanceDisposition indexHyperglycemic clampOverweight individualsGenetics of Plasminogen Activator Inhibitor-1 (PAI-1) in a Ghanaian Population
White MJ, Kodaman NM, Harder RH, Asselbergs FW, Vaughan DE, Brown NJ, Moore JH, Williams SM. Genetics of Plasminogen Activator Inhibitor-1 (PAI-1) in a Ghanaian Population. PLOS ONE 2015, 10: e0136379. PMID: 26322636, PMCID: PMC4556460, DOI: 10.1371/journal.pone.0136379.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Genetic variantsCircadian clock genesMost genetic studiesCardiovascular disease susceptibilityImportant genetic variantsActivator inhibitor-1Inhibitor-1Clock genesGenetic studiesGenetic effectsDisease susceptibilityArylsulfatase BMajor modulatorNovel associationsLack of overlapGenesPathway effectsMedian PAI-1European descentVariantsGeneticsPopulationSNPsCaucasian population
2012
Comparative Effects of Angiotensin Receptor Blockade and ACE Inhibition on the Fibrinolytic and Inflammatory Responses to Cardiopulmonary Bypass
Billings F, Balaguer J, Yu C, Wright P, Petracek M, Byrne J, Brown N, Pretorius M. Comparative Effects of Angiotensin Receptor Blockade and ACE Inhibition on the Fibrinolytic and Inflammatory Responses to Cardiopulmonary Bypass. Clinical Pharmacology & Therapeutics 2012, 91: 1065-1073. PMID: 22549281, PMCID: PMC3822756, DOI: 10.1038/clpt.2011.356.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsBenzimidazolesBiphenyl CompoundsBlood TransfusionBradykininCardiopulmonary BypassEndpoint DeterminationFemaleFibrinolysisHematocritHospital MortalityHumansInflammationInterleukinsLength of StayMaleMiddle AgedMonitoring, IntraoperativePerioperative CarePostoperative ComplicationsRamiprilTetrazolesTreatment OutcomeConceptsAngiotensin II type 1 receptor blockadeACE inhibitionCardiopulmonary bypassReceptor blockadeInflammatory responseType 1 receptor blockadeTissue-type plasminogen activator concentrationAngiotensin receptor blockadeEffect of angiotensinRed cell transfusionDay of surgeryPlasminogen activator inhibitor-1Activator inhibitor-1Plasminogen activator concentrationsHospital stayPlasma transfusionIL-10ACE inhibitorsIL-8Intraoperative fibrinolysisFibrinolysisInhibitor-1Comparative effectsPlaceboTransfusionDifferential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome
Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome. Hypertension 2012, 59: 893-898. PMID: 22353614, PMCID: PMC3402551, DOI: 10.1161/hypertensionaha.111.189589.Peer-Reviewed Original ResearchConceptsEffects of nebivololMetabolic syndromeBlood pressureInsulin sensitivityPlasminogen activator inhibitorAntagonist metoprololGlucose homeostasisThird-generation β-blockerActivator inhibitorMarkers of fibrinolysisCongestive heart failureDiastolic blood pressureLower blood pressureSystolic blood pressureCoronary artery diseaseGlucose tolerance testLarge clinical trialsDetrimental metabolic effectsPlasminogen activator inhibitor-1Insulin sensitivity indexAcute insulin responseΒ-cell functionActivator inhibitor-1Study drugArtery disease
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
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 migrationInhibitorsThrombosisDiabetesFibrosisPathogenesisFibrinolysisInjuryDisease
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
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-1Male–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 populationResponse to Letter Regarding Article, “Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass”
Pretorius M, Donahue B, Yu C, Greelish J, Roden D, Brown N. Response to Letter Regarding Article, “Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass”. Circulation 2008, 117: e170-e170. DOI: 10.1161/circulationaha.107.752386.Peer-Reviewed Original Research
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 morbidityA population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1.
Williams SM, Stocki S, Jiang L, Brew K, Gordon S, Vaughan DE, Brown NJ, Poku KA, Moore JH. A population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1. Ethnicity & Disease 2007, 17: 492-7. PMID: 17985503.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Tissue-type plasminogen activatorInter-individual variationGenetic architectureSignificant genetic componentGenetic analysisGenetic componentPhenotype informationPopulation-based studyPlasma t-PAActivator inhibitor-1Inhibitor-1Unrelated subjectsLarge-scale population-based studyStudy designChronic disease statusSystolic blood pressurePlasminogen activatorRisk of thrombosisProtein
2006
Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury
Ma J, Weisberg A, Griffin JP, Vaughan DE, Fogo AB, Brown NJ. Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury. Kidney International 2006, 69: 1064-1072. PMID: 16528256, DOI: 10.1038/sj.ki.5000201.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAldosteroneAnimalsBlood PressureChemokine CCL2CollagenFibronectinsGene ExpressionGlomerulonephritisHemodynamicsKidney GlomerulusMacrophagesMaleMiceMice, Inbred C57BLMice, Inbred StrainsMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1RNA, MessengerSialoglycoproteinsSodiumConceptsMonocyte chemoattractant protein-1Plasminogen activator inhibitor-1WT miceGlomerular injuryPlasminogen activator inhibitor-1 deficiencyCollagen IIIMRNA expressionPAI-1-deficient miceRenal collagen contentRenal osteopontin expressionSodium/potassium ratioUrine albumin excretionSystolic blood pressureRenal mRNA expressionChemoattractant protein-1Activator inhibitor-1Collagen IGrowth factor betaAlbumin excretionSodium excretionBlood pressureMesangial expansionRenal expressionCardiac injuryUrine volumeEndogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition
Brown NJ, Muldowney JA, Vaughan DE. Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition. Hypertension 2006, 47: 441-448. PMID: 16432054, DOI: 10.1161/01.hyp.0000202478.79587.1a.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsArginineDouble-Blind MethodDrug CombinationsEnzyme InhibitorsFemaleFibrinolysisHemodynamicsHumansInfusions, IntravenousMaleMiddle AgedNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlasminogen Activator Inhibitor 1ProdrugsRamiprilReference ValuesRenin-Angiotensin SystemConceptsPlasminogen activator inhibitor-1Plasminogen activator inhibitor-1 antigenActivator inhibitor-1Salt-replete subjectsL-arginineFibrinolytic balanceInhibitor-1Angiotensin-Converting Enzyme InhibitionNO precursor L-argininePlasminogen activator inhibitor antigenTissue-type plasminogen activator antigenEffect of angiotensinPrecursor L-argininePlasminogen activator antigenNO synthase inhibitorEnzyme inhibitionT-PA activityRenin activityD-dimerInhibitor antigenNormal subjectsSynthase inhibitorEnzyme inhibitorsT-PAAntigen
2005
Proteomic Patterns and Prediction of Glomerulosclerosis and Its Mechanisms
Xu BJ, Shyr Y, Liang X, Ma LJ, Donnert EM, Roberts JD, Zhang X, Kon V, Brown NJ, Caprioli RM, Fogo AB. Proteomic Patterns and Prediction of Glomerulosclerosis and Its Mechanisms. Journal Of The American Society Of Nephrology 2005, 16: 2967-2975. PMID: 16079267, DOI: 10.1681/asn.2005030262.Peer-Reviewed Original ResearchConceptsThymosin beta4Proteomic patternsProtein expression profilesSuch early eventsPlasminogen activator inhibitor-1 expressionMatrix-assisted laser desorption/ionization timeLaser desorption/ionization timeDesorption/ionization timeLaser capture microdissectionEndothelial cellsExpression profilesProtein profilesCapture microdissectionBeta4Cultured glomerular endothelial cellsPlasminogen activator inhibitor-1Early eventsFlight mass spectrometryIonization timeActivator inhibitor-1Inhibitor-1ProteinEarly activationMass spectrometryCells
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