2019
Androgens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor
Usselman CW, Yarovinsky T, Steele FE, Leone CA, Taylor HS, Bender JR, Stachenfeld NS. Androgens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor. The Journal Of Physiology 2019, 597: 2853-2865. PMID: 30847930, DOI: 10.1113/jp277756.Peer-Reviewed Original ResearchMeSH KeywordsAdultAndrogensCardiovascular DiseasesDihydrotestosteroneEndothelin-1Endothelium, VascularEstrogensEthinyl EstradiolFemaleGlucose Tolerance TestHumansMicrovesselsNitric OxideObesityPolycystic Ovary SyndromeReceptor, Endothelin BSkinVascular Endothelial Growth Factor AVasodilationYoung AdultConceptsPolycystic ovary syndromeCardiovascular dysfunctionEndothelial dysfunctionOvary syndromeEndothelin-1Endothelial functionNO productionAndrogen receptor-dependent mannerEndothelin-B receptor subtypeCardiovascular risk factorsMicrovascular endothelial dysfunctionMicrovascular endothelial functionCutaneous vascular conductanceB receptor subtypesEndothelin B receptorLaser Doppler flowmetryNitric oxide inhibitionReceptor-dependent mannerEndothelial cell NO productionDose-response curveVasodilating responsePCOS subjectsLean womenObese womenVascular conductance
2016
The molecular actions of oestrogen in the regulation of vascular health
Usselman CW, Stachenfeld NS, Bender JR. The molecular actions of oestrogen in the regulation of vascular health. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2016, 101: 356-361. PMID: 26778523, PMCID: PMC4947570, DOI: 10.1113/ep085148.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsEndothelium, VascularEstrogensFemaleHormone Replacement TherapyHumansMenopauseMuscle, Smooth, VascularConceptsAction of estrogenVascular healthFunctional outcomeHormone therapy trialsNormal endothelial functionVascular smooth muscleMembrane-bound estrogen receptorMolecular actionsPremenopausal womenEndothelial functionEstrogen actionCardiovascular diseaseEstrogen receptorSmooth muscleBeneficial actionsTherapy trialsEstrogenExperimental animalsVascular structuresFindings of studiesVasculatureWomenHealthMolecular mechanismsOutcomes
2014
Endothelial estrogen receptor isoforms and cardiovascular disease
Kim KH, Young BD, Bender JR. Endothelial estrogen receptor isoforms and cardiovascular disease. Molecular And Cellular Endocrinology 2014, 389: 65-70. PMID: 24530925, PMCID: PMC4040324, DOI: 10.1016/j.mce.2014.02.001.BooksMeSH KeywordsAnimalsCardiovascular DiseasesEndothelium, VascularEstrogensHumansProtein IsoformsReceptors, EstrogenSignal TransductionConceptsNitric oxideFull-length ERαPlasma membrane-associated estrogen receptorOvarian steroid hormonesMembrane-associated estrogen receptorsEstrogen receptor isoformsCardiovascular diseaseEstrogen receptorEndothelial responseRapid E2ER isoformsSteroid hormonesReceptor isoformsVascular cellsClinical contextFavorable effectTissue responseEndothelial signalingVascular systemERαER46Transcriptional modulationTransmembrane moleculesSignalingRapid endothelial responses
2013
Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. Journal Of Clinical Investigation 2013, 123: 5082-5097. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/jci67752.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBlood VesselsCadherinsCells, CulturedEar, ExternalEndothelium, VascularHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNeuropilinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2Retinal VesselsRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ZebrafishZebrafish ProteinsConceptsSmooth muscle cell-derived neuropilin-like proteinAberrant blood vessel formationNormal vascular developmentProtein tyrosineTC-PTPTransmembrane proteinTherapeutic targetBlood vessel formationVEGF responseNegative regulatorDevelopmental angiogenesisVEGFR-2Vascular developmentAttractive therapeutic targetESDNAngiogenesis regulationVE-cadherinVessel formationEC proliferationComplex formationRegulatorProteinNeuropilin expressionVEGF receptorsEndothelial VEGF
2008
Rac, PAK, and eNOS ACTion
Rao GK, Bender JR. Rac, PAK, and eNOS ACTion. Circulation Research 2008, 103: 328-330. PMID: 18703782, DOI: 10.1161/circresaha.108.182238.Peer-Reviewed Original ResearchVascular cell signaling by membrane estrogen receptors
Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008, 73: 864-869. PMID: 18325557, PMCID: PMC2519041, DOI: 10.1016/j.steroids.2008.01.008.Peer-Reviewed Original ResearchConceptsNumerous signal transduction cascadesEndothelial nitric oxide synthaseCaveolin-1 interactionSignal transduction cascadeEndothelial cellsNon-genomic actionsTranscriptional regulationPI3K/AktMembrane estrogen receptorsCaveolar membranesTransduction cascadeCell signalingC-SrcN-terminusHuman endothelial cellsRapid activationMolecular studiesConsequent activationVascular cellsNumerous animalsNitric oxideMultiple biological effectsEstrogen receptor alphaFavorable estrogenic effectsER46
2005
αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study
Zhang J, Krassilnikova S, Gharaei AA, Fassaei HR, Esmailzadeh L, Asadi A, Edwards DS, Harris TD, Azure M, Tellides G, Sinusas AJ, Zaret BL, Bender JR, Sadeghi MM. αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study. The FASEB Journal 2005, 19: 1857-1859. PMID: 16150802, DOI: 10.1096/fj.05-4130fje.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAutoradiographyCarotid Artery DiseasesCell MovementCell ProliferationCell TransplantationCells, CulturedChimeraCoronary VesselsDensitometryEndothelium, VascularHeart TransplantationHeterocyclic Compounds, 1-RingHumansImmunohistochemistryIntegrin alphaVbeta3Ki-67 AntigenLeukocytes, MononuclearMiceMice, SCIDMicroscopy, FluorescenceOrganometallic CompoundsRecombinant Fusion ProteinsTime FactorsTissue TransplantationUp-RegulationVascular DiseasesConceptsPeripheral blood mononuclear cellsGraft arteriopathyHuman coronary arteriesCoronary arteryAllogeneic human peripheral blood mononuclear cellsHuman/mouse chimeric modelAlphavbeta3 expressionHuman peripheral blood mononuclear cellsProliferative processesSevere combined immunodeficiency miceLate graft failureBlood mononuclear cellsCombined immunodeficiency miceAlphavbeta3 integrinSpecificity of uptakeCardiac transplantationConcentric narrowingGraft failureMononuclear cellsImmunodeficiency miceVascular remodelingNeointima formationNative aortaChimeric modelAutoradiographic studyRapid, Estrogen Receptor–Mediated Signaling: Why Is the Endothelium So Special?
Kim KH, Bender JR. Rapid, Estrogen Receptor–Mediated Signaling: Why Is the Endothelium So Special? Science Signaling 2005, 2005: pe28. PMID: 15956360, DOI: 10.1126/stke.2882005pe28.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCaveolaeCoronary DiseaseEndothelium, VascularEnzyme ActivationEstrogen Replacement TherapyFemaleHumansMaleMiddle AgedNitric OxideNitric Oxide Synthase Type IIIPostmenopausePremenopauseProtein IsoformsProto-Oncogene Proteins pp60(c-src)Randomized Controlled Trials as TopicReceptors, EstrogenSex DistributionSignal TransductionConceptsEstrogen receptorEndothelial NO synthaseNitric oxideEndothelial cellsHormone replacement therapyMembrane estrogen receptorsEndothelial activationVascular healthReplacement therapyCardiovascular diseaseVascular pathologyNO synthasePotent stimulusEstrogen responseFunctional alterationsENOS activationNongenomic responsesNO releaseRegulatory tissuesGenomic effectsCommon formProtective substancesMajor targetEndotheliumReceptors
2004
Detection of Injury-Induced Vascular Remodeling by Targeting Activated αvβ3 Integrin In Vivo
Sadeghi MM, Krassilnikova S, Zhang J, Gharaei AA, Fassaei HR, Esmailzadeh L, Kooshkabadi A, Edwards S, Yalamanchili P, Harris TD, Sinusas AJ, Zaret BL, Bender JR. Detection of Injury-Induced Vascular Remodeling by Targeting Activated αvβ3 Integrin In Vivo. Circulation 2004, 110: 84-90. PMID: 15210600, DOI: 10.1161/01.cir.0000133319.84326.70.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EArterial Occlusive DiseasesCarbocyaninesCarotid StenosisCell ProliferationCells, CulturedEndothelium, VascularFemaleHeterocyclic Compounds, 1-RingHumansIntegrin alphaVbeta3MiceMice, KnockoutOrganometallic CompoundsRadioactive TracersSulfonamidesTomography, Emission-Computed, Single-PhotonConceptsCounts/pixelCarotid areaCarotid artery wire injuryEndothelial cellsIntegrin expressionInjury-induced remodelingCell proliferationDetection of injuryVascular cell proliferationCultured endothelial cellsCarotid injuryBeta3 integrin expressionWire injuryVascular proliferationRP748Vascular remodelingApolipoprotein EKi67 stainingRenal clearanceEC bindingProliferation indexSpecific radiotracersInjuryProliferative processesWeeksVascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature
Sadeghi MM, Schechner JS, Krassilnikova S, Gharaei AA, Zhang J, Kirkiles-Smith N, Sinusas AJ, Zaret BL, Bender JR. Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature. Transplantation Proceedings 2004, 36: 1585-1591. PMID: 15251390, DOI: 10.1016/j.transproceed.2004.05.060.Peer-Reviewed Original ResearchConceptsChimeric human/mouse modelHuman/mouse modelHuman skin graftsEndothelial activationSkin graftsEndothelial cellsMouse modelIsotype-matched control antibodySCID/beige miceTumor necrosis factorEndothelial adhesion moleculesMurine VCAM-1Murine red blood cellsRed blood cellsHuman endothelial cellsControl antibodyInflammatory responseNecrosis factorBeige miceTc-99mVCAM-1Tissue vascularityMonoclonal antibodiesBlood cellsAdhesion molecules
2003
Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells
Li L, Haynes MP, Bender JR. Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 4807-4812. PMID: 12682286, PMCID: PMC153637, DOI: 10.1073/pnas.0831079100.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceCell LineCell MembraneCOS CellsEndothelium, VascularEstrogen Receptor alphaGenes, ReporterGenetic VariationHumansNitric Oxide SynthaseNitric Oxide Synthase Type IIIProtein Processing, Post-TranslationalReceptors, EstrogenRecombinant ProteinsRNA, MessengerSubcellular FractionsTranscriptional ActivationTransfectionConceptsPlasma membranePalmitoylation-dependent mannerPlasma membrane localizationInhibition of palmitoylationFull-length ER alphaReporter gene transactivationCOS-7 cellsEndothelial cell proteinsMembrane localizationAlternative splicingEstrogen receptor α variantsOestrogen receptor-alpha variantsN-terminusHuman endothelial cellsCell proteinsER46Synthase pathwayAcid labelingHy926 cellsNonendothelial cellsENOS activationENOS phosphorylationCellsEndothelial cellsMembrane
2002
Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*
Haynes MP, Li L, Sinha D, Russell KS, Hisamoto K, Baron R, Collinge M, Sessa WC, Bender JR. Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen*. Journal Of Biological Chemistry 2002, 278: 2118-2123. PMID: 12431978, DOI: 10.1074/jbc.m210828200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBlotting, WesternCell LineCells, CulturedElectrophoresis, Polyacrylamide GelEndoplasmic ReticulumEndothelium, VascularEnzyme ActivationEnzyme InhibitorsEstrogensHumansMiceMutationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesPhosphorylationPrecipitin TestsProtein BindingProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSrc-Family KinasesTime FactorsTransfectionTyrosineConceptsC-SrcPI3-kinaseAkt phosphorylationSrc kinaseUpstream regulatorKinase-dead c-SrcC-Src associationActive c-SrcC-Src phosphorylationMurine embryonic fibroblastsBasal Akt phosphorylationC-Src expressionCritical upstream regulatorEndothelial nitric oxide synthaseSrc familyActive AktEmbryonic fibroblastsComplex formation resultsEndothelial cellsHuman endothelial cellsAkt activationPhosphorylationKinaseAktPhosphatidylinositolRapid vascular cell responses to estrogen and membrane receptors
Haynes MP, Li L, Russell KS, Bender JR. Rapid vascular cell responses to estrogen and membrane receptors. Vascular Pharmacology 2002, 38: 99-108. PMID: 12379956, DOI: 10.1016/s0306-3623(02)00133-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneEndothelium, VascularEstrogensHumansMuscle, Smooth, VascularReceptors, EstrogenSignal TransductionConceptsSignal transduction cascadeTransduction cascadeG protein-coupled receptorsMembrane-localized estrogen receptorsEstrogen receptorTranscription factorsMAP kinaseApparent coronary heart diseaseRapid consequencesCellular responsesCellular localizationMembrane receptorsCoronary heart diseaseAge-matched malesEffects of estrogenVascular cell responsesSmooth muscle cellsVariety of estrogenVascular cellsMuscle cellsComplex formationPremenopausal womenHeart diseaseVascular wallMarked gender differencesEndothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit
Conte MS, VanMeter GA, Akst LM, Clemons T, Kashgarian M, Bender JR. Endothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit. Cardiovascular Research 2002, 53: 502-511. PMID: 11827702, DOI: 10.1016/s0008-6363(01)00486-2.Peer-Reviewed Original ResearchConceptsFinal lumen areaEndothelial cellsEndothelial restorationNeointimal areaLumen areaAutologous venous endothelial cellsLarger neointimal areaPositive remodeling indexBalloon catheter injuryTime of injuryHigh-grade stenosisCholesterol-fed rabbitsCholesterol-supplemented dietVessel wall repairVenous endothelial cellsIntact endothelial monolayerCatheter injuryRemodeling indexArterial injuryBalloon angioplastyIliofemoral arteriesContralateral vesselLuminal diameterVascular remodelingGrade stenosis
2001
Ex vivo evaluation of PBMNCs collected with a new cell separator
Snyder E, O'Donnell L, Dengler T, Pomper G, Velleca M, Dincecco D, Baril L, Min K, Gudino M, Bender J. Ex vivo evaluation of PBMNCs collected with a new cell separator. Transfusion 2001, 41: 940-949. PMID: 11452164, DOI: 10.1046/j.1537-2995.2001.41070940.x.Peer-Reviewed Original ResearchMeSH KeywordsBlood DonorsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DivisionCell SeparationCytotoxicity Tests, ImmunologicEndothelium, VascularE-SelectinHematopoietic Stem Cell TransplantationHumansInfant, NewbornKiller Cells, NaturalLeukapheresisLeukocytes, MononuclearTime FactorsUmbilical VeinsConceptsDendritic cellsNK cellsCell separatorHealthy volunteer blood donorsMNC subsetsEndothelial cellsVolunteer blood donorsB cell subsetsCell surface markersAmicus SeparatorNK cytotoxicityBlood donorsSelectin expressionAppropriate cell surface markersCD8CD4Ex vivoSurface markersCD19CD3Study designProliferation assaysSelectin inductionGrowth factorFunctional studiesINHIBITION OF INTERFERON-γ–MEDIATED MICROVASCULAR ENDOTHELIAL CELL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENE ACTIVATION BY HMG-COA REDUCTASE INHIBITORS1
Sadeghi M, Tiglio A, Sadigh K, O’Donnell L, Collinge M, Pardi R, Bender J. INHIBITION OF INTERFERON-γ–MEDIATED MICROVASCULAR ENDOTHELIAL CELL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENE ACTIVATION BY HMG-COA REDUCTASE INHIBITORS1. Transplantation 2001, 71: 1262-1268. PMID: 11397960, DOI: 10.1097/00007890-200105150-00014.Peer-Reviewed Original ResearchConceptsMicrovascular endothelial cellsClass II transactivatorInhibitory effectVascular diseaseSimvastatin pretreatmentIFN-gammaReductase inhibitorsClass II major histocompatibility complex moleculesCardiac transplant patientsGraft vascular diseaseLate graft failureHMG-CoA reductase inhibitorsHuman leukocyte antigenEffect of simvastatinMajor histocompatibility complex moleculesHLA-DR inductionSTAT-1 phosphorylationCoA reductase inhibitorsHistocompatibility complex moleculesHuman microvascular endothelial cellsInhibition of interferonTranscription-polymerase chain reaction analysisCardiac transplantationTransplant patientsGraft failure
2000
Membrane 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 involvementSimvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein
Sadeghi M, Collinge M, Pardi R, Bender J. Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein. The Journal Of Immunology 2000, 165: 2712-2718. PMID: 10946302, DOI: 10.4049/jimmunol.165.5.2712.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicBiological TransportCell Adhesion MoleculesCells, CulturedCholesterolCytokinesDrug SynergismEndothelium, VascularE-SelectinGene Expression RegulationGTP-Binding Protein alpha Subunits, Gi-GoHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1Interleukin-1NF-kappa BRNA, MessengerSignal TransductionSimvastatinSodium FluorideUmbilical VeinsVascular Cell Adhesion Molecule-1ConceptsEffect of simvastatinCytokine-induced expressionIL-1Endothelial CAMsEndothelial cell adhesion molecules E-selectinNF-kappaBProinflammatory cytokines IL-1Cell adhesion molecules E-selectinAdhesion molecules E-selectinPotent immune modulatorG protein activator NaFCytokines IL-1G protein-coupled pathwayInhibitory G proteinCytokine-mediated activationSelectin mRNA levelsBasal toneProinflammatory cytokinesGialpha proteinsImmune modulatorsTNF-alphaICAM-1Pertussis toxinE-selectinEndothelial responseMolecular mechanisms of estrogen actions on the vasculature
Haynes M, Russell K, Bender J. Molecular mechanisms of estrogen actions on the vasculature. Journal Of Nuclear Cardiology 2000, 7: 500-508. PMID: 11083200, DOI: 10.1067/mnc.2000.109958.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriosclerosisEndothelium, VascularEstrogensFemaleHormone Replacement TherapyHumansReceptors, EstrogenSignal TransductionTranscription, GeneticConceptsSelective estrogen receptor modulatorsEstrogen receptor modulatorsReceptor modulatorsPlaque-destabilizing effectsEffects of estrogenClinical atherosclerosisPharmacologic therapyVascular responsesMolecular mechanismsEstrogen actionVascular diseaseAnimal studiesBeneficial responseCardiovascular systemEstrogenVascular structuresAdverse effectsVasculatureSpecific pathwaysBroad spectrumAtherosclerosisHistologicInjuryTherapyDiseaseHuman vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling
Russell K, Haynes M, Sinha D, Clerisme E, Bender J. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 5930-5935. PMID: 10823945, PMCID: PMC18536, DOI: 10.1073/pnas.97.11.5930.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCell LineCell Membrane PermeabilityCells, CulturedCyclic GMPEndothelium, VascularEstradiolFlow CytometryHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNitric OxideReceptors, EstrogenRecombinant Fusion ProteinsSerum Albumin, BovineSignal TransductionTime FactorsTransfectionConceptsHuman endothelial cellsEstrogen receptorEndothelial cellsMitogen-activated protein kinaseER antagonist ICIHuman vascular endothelial cellsMembrane estrogen receptorsMembrane-impermeant formVascular endothelial cellsRapid intracellularRapid nongenomic responsesAntagonist ICIVascular functionE2 treatmentAcute effectsERalpha antibodyCGMP productionCardiovascular systemNongenomic responsesCytometric analysisEstrogen inducesGuanylate cyclaseRapid effectsNO releaseEarly effects