2016
Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease
Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ, Himmelfarb J, Ikizler TA, Brown NJ. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiological Reports 2016, 4: e12780. PMID: 27162261, PMCID: PMC4873632, DOI: 10.14814/phy2.12780.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedMitochondriaMuscle, SkeletalOxidative StressRenal Insufficiency, ChronicConceptsChronic kidney diseaseCKD stage 5Peripheral blood mononuclear cellsSeverity of CKDCKD stage 3Kidney diseaseOxidative stressF2-isoprostanesMtDNA copy numberMuscle biopsyMitochondrial volume densitySkeletal muscleDifferent CKD stagesMitochondrial dysfunctionBlood mononuclear cellsStage 3Stage 5Skeletal muscle biopsiesLower mtDNA copy numberMitochondrial DNA copy numberPlasma isofuransCKD stageMuscle dysfunctionMononuclear cellsFunction worsens
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
Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonism
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
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
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 volume
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 II
2002
Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Schoenhard JA, Painter CA, Ripley RT, Brown NJ, Fogo AB, Vaughan DE. Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition. Journal Of Molecular And Cellular Cardiology 2002, 34: 617-627. PMID: 12054849, DOI: 10.1006/jmcc.2002.2001.Peer-Reviewed Original ResearchConceptsSystolic blood pressureNitric oxide synthase inhibitionOxide synthase inhibitionPerivascular fibrosisBlood pressurePAI-1 deficiencyCoronary perivascular fibrosisPlasminogen activator systemL-NAMENOS inhibitionSynthase inhibitionDeficient miceVascular pathologyLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterL-NAME-induced hypertensionLong-term NOS inhibitionPlasma TGF-beta1 levelsPlasminogen activator inhibitor-1-deficient miceStructural vascular changesTGF-beta1 levelsLong-term treatmentTissue-type plasminogen activator-deficient miceWeek study periodActivator system
2001
Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Fogo A, Ma L, Schoenhard J, Brown N, Vaughan D. Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition. Circulation 2001, 104: 839-844. PMID: 11502712, DOI: 10.1161/hc3301.092803.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureBody WeightCollagenCoronary VesselsEnzyme InhibitorsFibrosisHemodynamicsHypertensionHypertrophy, Left VentricularMaleMiceMice, Inbred C57BLMice, KnockoutNG-Nitroarginine Methyl EsterNitric Oxide SynthasePlasminogen Activator Inhibitor 1Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerTimeConceptsPlasminogen activator inhibitor-1Systolic blood pressureLong-term NOS inhibitionBlood pressurePAI-1 deficiencyNitric oxide synthaseCoronary perivascular fibrosisPerivascular fibrosisNOS inhibitionWT miceLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterNitric oxide synthase inhibitionWild-type male miceControl WT miceStructural vascular changesOxide synthase inhibitionArteriosclerotic cardiovascular diseaseDevelopment of fibrosisPAI-1 activityNew therapeutic strategiesActivator inhibitor-1Cardiac type ILong-term inhibitionPrevents hypertension