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
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
2013
Contribution 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
Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial
Balaguer JM, Yu C, Byrne JG, Ball SK, Petracek MR, Brown NJ, Pretorius M. Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial. Clinical Pharmacology & Therapeutics 2012, 93: 326-334. PMID: 23361105, PMCID: PMC4031681, DOI: 10.1038/clpt.2012.249.Peer-Reviewed Original ResearchConceptsBradykinin B2 receptor antagonismB2 receptor antagonismCardiopulmonary bypassEndogenous bradykininTissue-type plasminogen activatorHoe 140Receptor antagonismBradykinin B2 receptor antagonistSubsequent transfusion requirementsBlood product transfusionProportion of patientsB2 receptor antagonistD-dimer concentrationD-dimer formationEACA treatmentTransfusion requirementsPostoperative bleedingProduct transfusionBlood lossCardiac surgeryInflammatory cytokinesReceptor antagonistClinical trialsFibrinolytic capacityInflammatory responseAldosterone 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 injuryComparative 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 effectsPlaceboTransfusion
2011
Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis
Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ. Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis. Journal Of The American Society Of Nephrology 2011, 23: 334-342. PMID: 22158433, PMCID: PMC3269170, DOI: 10.1681/asn.2011030287.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsBlood CoagulationCD40 LigandCross-Over StudiesCytokinesDouble-Blind MethodFemaleHemodynamicsHumansInflammationKidney Failure, ChronicMaleMiddle AgedOxidative StressRamiprilRenal DialysisReninTetrazolesValineValsartanConceptsAngiotensin receptor blockersMaintenance hemodialysis patientsCardiovascular mortalityHemodialysis patientsACE inhibitorsGreater anti-inflammatory effectAngiotensin-Converting Enzyme InhibitionOxidative stressAngiotensin receptor blockadeIL-10 concentrationsD-dimer levelsIL-6 levelsProspective clinical trialsAnti-inflammatory effectsIL-1β concentrationsLevels of vWFSerial blood samplingCardiovascular eventsEndothelial dysfunctionCrossover studyWashout periodIsoprostane levelsClinical trialsDrug treatmentVWF levels
2010
Aldosterone 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
2008
Aldosterone 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
2005
The Kallikrein-Kinin System: Current and Future Pharmacological Targets
Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A. The Kallikrein-Kinin System: Current and Future Pharmacological Targets. Journal Of Pharmacological Sciences 2005, 99: 6-38. PMID: 16177542, DOI: 10.1254/jphs.srj05001x.Peer-Reviewed Original ResearchMeSH KeywordsAngioedemaAngiotensin-Converting Enzyme InhibitorsAnimalsAprotininBradykininBradykinin B2 Receptor AntagonistsCardiovascular DiseasesComplement C1 Inactivator ProteinsComplement C1 Inhibitor ProteinHumansInflammationKallikrein-Kinin SystemKallikreinsKidney DiseasesKininsNeprilysinPeptidyl-Dipeptidase APolymorphism, GeneticPyridinesRandomized Controlled Trials as TopicReceptor, Bradykinin B1Receptor, Bradykinin B2SerpinsThiazepinesConceptsKallikrein-kinin systemMultiple pharmacological interventionsPrecursors of kininsFuture pharmacological targetsProinflammatory effectsVasoactive kininsPharmacological interventionsCardiovascular propertiesPharmacological targetsComplement pathwayKininsActive kininsPathological processesPharmacological activitiesPlasma kallikreinMetabolic cascadeImportant metabolic pathwaysMetabolic pathwaysAntiproteases
2004
Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events
Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events. Circulation 2004, 109: iv-6-iv-19. PMID: 15226246, DOI: 10.1161/01.cir.0000133444.17867.56.Peer-Reviewed Original Research
2000
Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans.
Kim KS, Kumar S, Simmons WH, Brown NJ. Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans. Journal Of Pharmacology And Experimental Therapeutics 2000, 292: 295-8. PMID: 10604961.Peer-Reviewed Original ResearchConceptsDegradation of bradykininACE inhibitionWheal responseACE inhibitor quinaprilEffect of quinaprilNon-ACE pathwaysMetabolism of bradykininDose-response curveCardioprotective effectsIntradermal administrationIntradermal injectionOral administrationHealthy subjectsEnzyme inhibitorsSignificant interactionQuinaprilBradykininAminopeptidase PAngiotensinInhibitionAdministrationHuman skinPresent studyApstatinResponse