2022
Targeting the vasculature in cardiometabolic disease
Boutagy NE, Singh AK, Sessa WC. Targeting the vasculature in cardiometabolic disease. Journal Of Clinical Investigation 2022, 132: e148556. PMID: 35289308, PMCID: PMC8920329, DOI: 10.1172/jci148556.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAtherosclerosisCardiovascular DiseasesDiabetes Mellitus, Type 2Endothelium, VascularHumansInsulin ResistanceObesityConceptsCardiometabolic diseasesCardiometabolic disease burdenOptimal medical therapyType 2 diabetesContext of atherosclerosisCardiometabolic changesCV morbidityEndothelial dysfunctionEjection fractionGlycemic controlHeart failureMedical therapyProinflammatory mediatorsVascular inflammationDisease burdenDisease progressionCardiovascular diseaseVascular remodelingPathological changesEpidemic proportionsVascular endotheliumMetabolic diseasesDiseaseVasculatureObesity
2001
Akt-Mediated Phosphorylation of the G Protein-Coupled Receptor EDG-1 Is Required for Endothelial Cell Chemotaxis
Lee M, Thangada S, Paik J, Sapkota G, Ancellin N, Chae S, Wu M, Morales-Ruiz M, Sessa W, Alessi D, Hla T. Akt-Mediated Phosphorylation of the G Protein-Coupled Receptor EDG-1 Is Required for Endothelial Cell Chemotaxis. Molecular Cell 2001, 8: 693-704. PMID: 11583630, DOI: 10.1016/s1097-2765(01)00324-0.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell LineChemotaxisEndothelium, VascularEnzyme ActivationHumansImmediate-Early ProteinsLysophospholipidsModels, BiologicalNeovascularization, PhysiologicPhosphorylationProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRac GTP-Binding ProteinsReceptors, Cell SurfaceReceptors, G-Protein-CoupledReceptors, LysophospholipidRecombinant Fusion ProteinsSignal TransductionSphingosineConceptsG protein-coupled receptor Edg-1EDG-1Cell migrationRac activationAkt-Mediated PhosphorylationCortical actin assemblyProtein kinase AktThird intracellular loopAkt bindsActin assemblyEndothelial cell migrationKinase AktSpecificity switchEndothelial cell chemotaxisCellular phenomenaDependent signalingIntracellular loopAktCell chemotaxisTransactivationPhosphorylationGPCRsChemotaxisActivationMutantsAkt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*
Gratton J, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa W. Akt Down-regulation of p38 Signaling Provides a Novel Mechanism of Vascular Endothelial Growth Factor-mediated Cytoprotection in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 30359-30365. PMID: 11387313, DOI: 10.1074/jbc.m009698200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisBlotting, WesternCattleCell DeathCell LineCell SurvivalCells, CulturedDose-Response Relationship, DrugDown-RegulationEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationEnzyme InhibitorsFlow CytometryHumansImidazolesLymphokinesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktPyridinesSignal TransductionTime FactorsUmbilical VeinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsMEKK3 phosphorylationP38 activationMEKK3 kinase activityMitogen-activated protein kinaseP38 mitogen-activated protein kinaseP38-dependent apoptosisP38 MAPK inhibitor SB203580Dominant-negative RacInhibition of PIActivation of MKK3/6Vascular endothelial growth factorMAPK inhibitor SB203580P38 MAPK pathwayP38 MAPK activationEndothelial cellsEndothelial cell survivalGrowth factorRac activationProtein kinaseActive AktPro-apoptotic effectsKinase activityInhibitor SB203580MAPK activationP38 signalingCan modulation of endothelial nitric oxide synthase explain the vasculoprotective actions of statins?
Sessa W. Can modulation of endothelial nitric oxide synthase explain the vasculoprotective actions of statins? Trends In Molecular Medicine 2001, 7: 189-191. PMID: 11325618, DOI: 10.1016/s1471-4914(01)01985-2.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseMainstay of therapyCoronary artery diseaseLipid-lowering effectsNitric oxide synthaseNitric oxide synthesisClass of drugsNitric oxide releaseArtery diseaseVasculoprotective actionsOxide synthaseBeneficial actionsOxide synthesisOxide releaseCellular mechanismsStatinsDrugsRecent insightsTherapyMainstayDiseaseSuppression of Vascular Endothelial Growth Factor-Mediated Endothelial Cell Protection by Survivin Targeting
Mesri M, Morales-Ruiz M, Ackermann E, Bennett C, Pober J, Sessa W, Altieri D. Suppression of Vascular Endothelial Growth Factor-Mediated Endothelial Cell Protection by Survivin Targeting. American Journal Of Pathology 2001, 158: 1757-1765. PMID: 11337373, PMCID: PMC1891951, DOI: 10.1016/s0002-9440(10)64131-4.Peer-Reviewed Original ResearchApoptosisCell MovementCells, CulturedDNADNA, AntisenseDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularGene Expression RegulationHumansInhibitor of Apoptosis ProteinsLymphokinesMicrotubule-Associated ProteinsNeoplasm ProteinsProteinsRNA, MessengerSurvivinVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsHeat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*
Pritchard K, Ackerman A, Gross E, Stepp D, Shi Y, Fontana J, Baker J, Sessa W. Heat Shock Protein 90 Mediates the Balance of Nitric Oxide and Superoxide Anion from Endothelial Nitric-oxide Synthase*. Journal Of Biological Chemistry 2001, 276: 17621-17624. PMID: 11278264, DOI: 10.1074/jbc.c100084200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcimycinCattleCells, CulturedEndothelium, VascularHSP90 Heat-Shock ProteinsIonophoresNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIConceptsEndothelial nitric oxide synthaseBovine coronary endothelial cellsNitric oxide synthaseHeat shock protein 90Shock protein 90Nitric oxidePhospho-eNOS levelsCoronary endothelial cellsProtein 90ENOS activityAssociation of hsp90Calcium ionophoreEndothelial cellsNitrite productionVascular biologySuperoxide anionAssociationPretreatmentHsp90SynthaseSphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*
Morales-Ruiz M, Lee M, Zöllner S, Gratton J, Scotland R, Shiojima I, Walsh K, Hla T, Sessa W. Sphingosine 1-Phosphate Activates Akt, Nitric Oxide Production, and Chemotaxis through a GiProtein/Phosphoinositide 3-Kinase Pathway in Endothelial Cells*. Journal Of Biological Chemistry 2001, 276: 19672-19677. PMID: 11278592, DOI: 10.1074/jbc.m009993200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, NorthernBlotting, WesternCattleCell MovementChemotaxisCulture Media, Serum-FreeDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularEnzyme ActivationGenes, DominantGTP-Binding Protein alpha Subunits, Gi-GoLungLymphokinesLysophospholipidsNeovascularization, PhysiologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceSignal TransductionSphingosineTime FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVirulence Factors, BordetellaConceptsEndothelial differentiation gene familySerine/threonine kinase AktHeterotrimeric G proteinsThreonine kinase AktEDG-1 receptorGene familyAkt substrateKinase AktEndothelial cell chemotaxisActivates AktENOS phosphorylationAkt activationG proteinsCell survivalEndothelial nitric oxide synthasePhosphorylationAktCell chemotaxisSppSignalingGrowth factorVascular endothelial growth factorChemotaxisEndothelial cellsSphingosine
2000
Direct Interaction between Endothelial Nitric-oxide Synthase and Dynamin-2 IMPLICATIONS FOR NITRIC-OXIDE SYNTHASE FUNCTION*
Cao S, Yao J, McCabe T, Yao Q, Katusic Z, Sessa W, Shah V. Direct Interaction between Endothelial Nitric-oxide Synthase and Dynamin-2 IMPLICATIONS FOR NITRIC-OXIDE SYNTHASE FUNCTION*. Journal Of Biological Chemistry 2000, 276: 14249-14256. PMID: 11120737, DOI: 10.1074/jbc.m006258200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaBlotting, WesternCalcimycinCattleCell LineDose-Response Relationship, DrugDynamin IDynaminsEndothelium, VascularGlutathione TransferaseGolgi ApparatusGTP PhosphohydrolasesIonophoresKineticsMicroscopy, ConfocalMicroscopy, FluorescenceNitric Oxide SynthaseNitric Oxide Synthase Type IIIPrecipitin TestsProtein BindingProtein BiosynthesisRatsRecombinant Fusion ProteinsTransfectionConceptsDynamin 2Bovine aortic endothelial cellsRecombinant eNOS proteinDirect protein-protein interactionDouble-label confocal immunofluorescenceProtein-protein interactionsSpecific protein interactionsDirect interactionClone 9 cellsEndothelial nitric oxide synthaseMembrane compartmentsLarge GTPaseGlutathione S-transferaseProtein interactionsNovel functionDynaminECV-304 cellsSynthase functionIntracellular signalsMembrane distributionConfocal immunofluorescenceFluorescent proteinENOS regulationGreen fluorescentProteinSimvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs
Mital S, Zhang X, Zhao G, Bernstein R, Smith C, Fulton D, Sessa W, Liao J, Hintze T. Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs. AJP Heart And Circulatory Physiology 2000, 279: h2649-h2657. PMID: 11087217, DOI: 10.1152/ajpheart.2000.279.6.h2649.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdenosineAnimalsAnticholesteremic AgentsConsciousnessCoronary CirculationDogsEndothelium, VascularEnzyme InhibitorsGene Expression Regulation, EnzymologicHeart RateIn Vitro TechniquesMicrocirculationMyocardiumNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIINitritesNitroglycerinOxygen ConsumptionRNA, MessengerSimvastatinVasodilationVasodilator AgentsVeratrineConceptsEndothelial nitric oxide synthaseCoronary blood flowCoronary vasodilationConscious dogsSimvastatin administrationVascular endothelial nitric oxide productionVascular endothelial nitric oxide synthaseNO productionEndothelial nitric oxide productionEndothelium-independent vasodilatorCoronary vascular endotheliumShort-term administrationLipid-lowering effectsNitric oxide synthaseEndothelial NO productionMyocardial oxygen consumptionNitric oxide productionNO-dependent regulationPlasma nitrateGeneral anesthesiaENOS proteinCoronary microvesselsOxide synthaseMongrel dogsENOS mRNAMembrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells
Haynes M, Sinha D, Russell K, Collinge M, Fulton D, Morales-Ruiz M, Sessa W, Bender J. Membrane Estrogen Receptor Engagement Activates Endothelial Nitric Oxide Synthase via the PI3-Kinase–Akt Pathway in Human Endothelial Cells. Circulation Research 2000, 87: 677-682. PMID: 11029403, DOI: 10.1161/01.res.87.8.677.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeBinding SitesCell MembraneCells, CulturedChromonesEndothelium, VascularEnzyme InhibitorsEstradiolGenes, DominantHumansMorpholinesNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSerum Albumin, BovineSignal TransductionTransduction, GeneticConceptsPI3-kinaseKinase-Akt pathwayDominant-negative AktPI3-kinase inhibitorRapid eNOS phosphorylationRapid Akt phosphorylationActivation of eNOSAkt-dependent pathwayEndothelial nitric oxide synthaseAkt substratePhosphatidylinositol 3ENOS phosphorylationCritical residuesSerine 473Human endothelial cellsEstrogen receptor antagonist ICI 182Cell membrane sitesHuman endothelial cell lineAkt pathwayAkt phosphorylationPhosphorylationReceptor engagementEndothelial cell lineActivation eventsFunctional involvementThe HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer D, Sessa W, Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Medicine 2000, 6: 1004-1010. PMID: 10973320, PMCID: PMC2828689, DOI: 10.1038/79510.Peer-Reviewed Original ResearchConceptsProtein kinase Akt/PKBKinase Akt/PKBProtein kinase AktAkt/PKBAkt-dependent mannerVascular structure formationActivation of AktKinase AktVascular endothelial growth factor treatmentEnhanced phosphorylationBlood vessel growthNew blood vessel growthAktGrowth factor treatmentVessel growthEndothelial cellsEndothelial nitric oxide synthaseRecent studiesHMG-CoA reductase inhibitor simvastatinAngiogenesisPKBFactor treatmentPhosphorylationReductase inhibitor simvastatinApoptosisAcute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo
Luo Z, Fujio Y, Kureishi Y, Rudic R, Daumerie G, Fulton D, Sessa W, Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo. Journal Of Clinical Investigation 2000, 106: 493-499. PMID: 10953024, PMCID: PMC380252, DOI: 10.1172/jci9419.Peer-Reviewed Original ResearchConceptsDN-AktEndothelial cell nitric oxide synthaseMyr-AktSerine/threonine protein kinase AktProtein kinase AktDominant-negative AktNitric oxideVasomotor toneFemoral arteryAkt functionReplication-defective adenoviral constructKinase AktActive AktEndothelium-dependent vasodilatationKey regulatorEndothelium-independent vasodilatorEndothelium-dependent vasomotionRabbit femoral artery modelNitric oxide synthaseAorta ex vivoImportant regulatorGene transferDoppler flow measurementsAktENOS inhibitorReconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*
Gratton J, Fontana J, O'Connor D, Garcı́a-Cardeña G, McCabe T, Sessa W. Reconstitution of an Endothelial Nitric-oxide Synthase (eNOS), hsp90, and Caveolin-1 Complex in Vitro EVIDENCE THAT hsp90 FACILITATES CALMODULIN STIMULATED DISPLACEMENT OF eNOS FROM CAVEOLIN-1*. Journal Of Biological Chemistry 2000, 275: 22268-22272. PMID: 10781589, DOI: 10.1074/jbc.m001644200.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAssociation of eNOSNitric oxide synthaseLung microvascular endothelial cellsCaveolin-1Microvascular endothelial cellsENOS enzymatic activityAction of CaMBovine lung microvascular endothelial cellsENOS functionCalcium-activated calmodulinConcentration of CaMShock protein 90Addition of CaMEndothelial cellsVitro EvidenceCav-1Protein 90AssociationPresence of Hsp90Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt
Morales-Ruiz M, Fulton D, Sowa G, Languino L, Fujio Y, Walsh K, Sessa W. Vascular Endothelial Growth Factor–Stimulated Actin Reorganization and Migration of Endothelial Cells Is Regulated via the Serine/Threonine Kinase Akt. Circulation Research 2000, 86: 892-896. PMID: 10785512, DOI: 10.1161/01.res.86.8.892.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCattleCell MovementCells, CulturedCytoskeletonEndothelium, VascularProtein Serine-Threonine KinasesSignal TransductionConceptsSignal transduction mechanismsCell migrationActin reorganizationActive AktMyr-AktSerine/threonine kinase AktCell signal transduction mechanismsTransduction mechanismsThreonine kinase AktVascular endothelial growth factorDominant-negative AktDistinct signal transduction mechanismsBovine lung microvascular endothelial cellsEndothelial cellsAbsence of VEGFActin cytoskeletonGrowth factorMicrovascular endothelial cellsKinase AktActin rearrangementStress fibersF-actinCell locomotionEndothelial growth factorEndothelial cell proliferationAngiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*
Papapetropoulos A, Fulton D, Mahboubi K, Kalb R, O'Connor D, Li F, Altieri D, Sessa W. Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*. Journal Of Biological Chemistry 2000, 275: 9102-9105. PMID: 10734041, DOI: 10.1074/jbc.275.13.9102.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1AnimalsApoptosisCattleCells, CulturedEndothelium, VascularFlow CytometryInhibitor of Apoptosis ProteinsMembrane GlycoproteinsMicrotubule-Associated ProteinsNeoplasm ProteinsPhosphorylationProtein Serine-Threonine KinasesProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSurvivinConceptsAkt/survivin pathwaySerine-threonine kinaseDeath-inducing stimuliPost-natal angiogenesisDominant-negative survivinEndothelial cellsEndothelial cell survivalAnti-apoptotic pathwaysSurvival machineryEndothelial cell apoptosisSurvivin pathwayApoptosis inhibitorCell survivalCell apoptosisVascular stabilizationAktSurvivinTie-2 receptorAngiogenic responseApoptosisCellsPathwayAngiogenesisMorphogenesisKinaseEstrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*
Russell K, Haynes M, Caulin-Glaser T, Rosneck J, Sessa W, Bender J. Estrogen Stimulates Heat Shock Protein 90 Binding to Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells EFFECTS ON CALCIUM SENSITIVITY AND NO RELEASE*. Journal Of Biological Chemistry 2000, 275: 5026-5030. PMID: 10671543, DOI: 10.1074/jbc.275.7.5026.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNitric oxide synthaseHuman umbilical vein endothelial cellsENOS activationOxide synthaseEstrogen receptor antagonist ICINO releaseEndothelium-dependent vasodilationReceptor-mediated modulationReceptor antagonist ICINitric oxide releaseUmbilical vein endothelial cellsVein endothelial cellsAntagonist ICIHeat shock protein 90CGMP productionShock protein 90Oxide releaseEndothelial cellsEndothelial cell effectsCalcium sensitivityCalcium dependenceCell effectsEstrogenProtein 90
1999
Trafficking of Endothelial Nitric-oxide Synthase in Living Cells QUANTITATIVE EVIDENCE SUPPORTING THE ROLE OF PALMITOYLATION AS A KINETIC TRAPPING MECHANISM LIMITING MEMBRANE DIFFUSION*
Sowa G, Liu J, Papapetropoulos A, Rex-Haffner M, Hughes T, Sessa W. Trafficking of Endothelial Nitric-oxide Synthase in Living Cells QUANTITATIVE EVIDENCE SUPPORTING THE ROLE OF PALMITOYLATION AS A KINETIC TRAPPING MECHANISM LIMITING MEMBRANE DIFFUSION*. Journal Of Biological Chemistry 1999, 274: 22524-22531. PMID: 10428829, DOI: 10.1074/jbc.274.32.22524.Peer-Reviewed Original ResearchConceptsPlasma membraneENOS-GFPFluorescent protein fusion constructsProtein-protein interactionsRole of palmitoylationProtein fusion constructsLipid bilayersRate of traffickingEndothelial cell line ECV304Endothelial nitric oxide synthasePalmitoylation stateCellular domainsFusion constructsPerinuclear regionLiving cellsProtein diffusionFluorescence recoveryRegulation of eNOSMembrane markersPalmitoylationMutantsGolgiTraffickingMembrane diffusionEndothelial cellsRegulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton D, Gratton J, McCabe T, Fontana J, Fujio Y, Walsh K, Franke T, Papapetropoulos A, Sessa W. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999, 399: 597-601. PMID: 10376602, PMCID: PMC3637917, DOI: 10.1038/21218.Peer-Reviewed Original ResearchConceptsProtein kinase AktKinase AktSerine/threonine protein kinase AktMutant eNOSRole of phosphorylationEndothelial nitric oxide synthaseSerine 1179Akt substrateSignal transductionGene transferAktAdenovirus-mediated gene transferPhosphorylationGrowth factorVascular endothelial growth factorEndothelial cellsRegulationSynthase isoformsEndothelial growth factorNitric oxide productionTransductionVascular remodellingOxide productionIsoformsProductionNO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats
Wiest R, Shah V, Sessa W, Groszmann R. NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. American Journal Of Physiology 1999, 276: g1043-g1051. PMID: 10198349, DOI: 10.1152/ajpgi.1999.276.4.g1043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Flow VelocityBlood PressureEndothelium, VascularHypertension, PortalKineticsLuminescent MeasurementsMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroarginineRatsRats, Sprague-DawleySplanchnic CirculationStress, MechanicalConceptsHyperdynamic splanchnic circulationSuperior mesenteric arterySplanchnic circulationSham ratsNitric oxide synthase upregulationHyperdynamic circulatory syndromeNO metabolites concentrationPortal hypertensive ratsENOS protein levelsHigh blood flowSignificant hyporesponsivenessArterial vasodilatationL-NNAPortal hypertensionPVL ratsAgonist methoxamineCirculatory syndromeENOS upregulationHypertensive ratsMesenteric arteryNomega-nitroNO inhibitorBlood flowDay 3L-arginineA vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase
Guillot P, Guan J, Liu L, Kuivenhoven J, Rosenberg R, Sessa W, Aird W. A vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase. Journal Of Clinical Investigation 1999, 103: 799-805. PMID: 10079100, PMCID: PMC408151, DOI: 10.1172/jci6017.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthase geneEndothelial nitric oxide synthaseMurine endothelial progenitor cellsGrowth factor antibodyNitric oxide synthase geneNitric oxide synthaseEndothelial progenitor cellsOxide synthase geneFactor antibodyOxide synthaseVascular bedResponse elementCardiac expressionTransgenic micePDGF-ABCardiac endotheliumEno expressionCardiac myocytesSkeletal muscleProgenitor cellsSkeletal myocytesEndotheliumMiceBrainBeta-galactosidase activity