2014
Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis
Mehra VC, Jackson E, Zhang XM, Jiang XC, Dobrucki LW, Yu J, Bernatchez P, Sinusas AJ, Shulman GI, Sessa WC, Yarovinsky TO, Bender JR. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis. American Journal Of Pathology 2014, 184: 1562-1576. PMID: 24606881, PMCID: PMC4005977, DOI: 10.1016/j.ajpath.2014.01.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaArteriesCattleCeramidesDiet, High-FatEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesHaploinsufficiencyHindlimbHumansIschemiaMice, Inbred C57BLNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPalmitic AcidPhosphorylationProtein Phosphatase 2Proto-Oncogene Proteins c-aktSerine C-PalmitoyltransferaseSignal TransductionVascular Endothelial Growth Factor AConceptsPP2A inhibitor okadaic acidProtein phosphatase 2AInhibitor okadaic acidVEGF-induced signalingSerine palmitoyltransferase inhibitor myriocinDe novo ceramide synthesisPhosphatase 2AENOS agonistsNovo ceramide synthesisPalmitic acidAngiogenic responsePotential molecular targetsOkadaic acidEndothelial cellsEarly speciesEndothelial cell responsesCord formationVEGFR2 phosphorylationSaturated free fatty acidVEGF resistanceCeramide synthesisResistance mechanismsMolecular targetsVascular homeostasisPhosphorylation
2009
Membrane-initiated actions of estrogen on the endothelium
Kim KH, Bender JR. Membrane-initiated actions of estrogen on the endothelium. Molecular And Cellular Endocrinology 2009, 308: 3-8. PMID: 19549586, PMCID: PMC2701909, DOI: 10.1016/j.mce.2009.03.025.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseNumerous signal transduction cascadesSignal transduction cascadeNitric oxideEndothelial cellsNon-genomic actionsAction of estrogenNitric oxide synthaseCaveolar membranesEstrogen receptor alphaTransduction cascadeC-SrcN-terminusShort isoformHuman endothelial cellsRapid activationProduct nitric oxideVascular studiesOxide synthaseReceptor alphaEstrogenVascular structuresER46Favorable effectCritical role
2008
Vascular 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
2007
Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation
Li L, Hisamoto K, Kim KH, Haynes MP, Bauer PM, Sanjay A, Collinge M, Baron R, Sessa WC, Bender JR. Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 16468-16473. PMID: 17921256, PMCID: PMC2034248, DOI: 10.1073/pnas.0704315104.Peer-Reviewed Original ResearchConceptsC-SrcC-Src kinase activityTyrosine kinase c-SrcRapid signal transductionKinase c-SrcC-Src functionC-Src kinaseEndothelial NO synthase activationENOS activationMembrane recruitmentSignal transductionComplex assemblyPlasma membraneKinase activityOestrogen receptor-alpha variantsVenous endothelial cellsER46Pathway activationHormonal stimuliCritical roleArterial responseNO synthase activationSynthase activationStructural requirementsEndothelial cells
2005
Rapid, 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 cellsMembraneEstrogen-Stimulated, Membrane-Initiated Receptor-Ligand Interactions in Vascular Cells
Lei L, Haynes M, Bender J. Estrogen-Stimulated, Membrane-Initiated Receptor-Ligand Interactions in Vascular Cells. 2003, 37-45. DOI: 10.1007/978-1-4615-0339-2_5.Peer-Reviewed Original ResearchEndothelial nitric oxide synthaseNitric oxideEndothelial cellsNitric oxide synthaseMembrane estrogen receptorsVascular endothelial cellsEndothelial dysfunctionOxide synthaseEstrogen receptorChronic activationVascular endotheliumLuminal liningPathology 1Vascular cellsMental healthBlood vesselsProtective actionHomeostatic stateReceptorsPivotal rolePertinent chaptersVast majorityCellsDysfunctionReversible phase
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 activationPhosphorylationKinaseAktPhosphatidylinositolEndothelial 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 studies
2000
Human 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 effectsEstrogen 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
1998
Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion.
Collinge M, Pardi R, Bender J. Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion. The Journal Of Immunology 1998, 161: 1589-93. PMID: 9712019, DOI: 10.4049/jimmunol.161.4.1589.Peer-Reviewed Original ResearchConceptsClass II transactivatorNK cellsIFN-gamma-dependent mechanismIFN-gamma-independent mannerLymphocyte adhesionMHC class II expressionHLA-DR alpha mRNAHLA-DR expressionMHC class II moleculesNK cell activationAllogeneic endothelial cellsClass II expressionIFN-gamma-induced MHC class II expressionClass II moleculesAlpha mRNA expressionCell linesHLA-DRIFN-gammaCell activationMRNA expressionEndothelial cellsAlpha mRNACellsPromoter constructsActivationRetroviral Gene Transfer: Effects on Endothelial Cell Phenotype
Inaba M, Toninelli E, Vanmeter G, Bender J, Conte M. Retroviral Gene Transfer: Effects on Endothelial Cell Phenotype. Journal Of Surgical Research 1998, 78: 31-36. PMID: 9733614, DOI: 10.1006/jsre.1998.5379.Peer-Reviewed Original ResearchConceptsEndothelial cellsTransduced ECsCell adhesion molecule profilesCell phenotypeHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsAdhesion molecule profileUpregulation of expressionGT protocolVein endothelial cellsTarget cell phenotypeViral exposureMHC-IICardiovascular diseaseActivation moleculeICAM-1Endothelial cell phenotypeVCAM-1E-selectinGene transferVivo gene transferCell countSystemic deliveryCytokine stimulationUnaltered patternInduction of transporter associated with antigen processing by interferon γ confers endothelial cell cytoprotection against natural killer-mediated lysis
Ayalon O, Hughes E, Cresswell P, Lee J, O’Donnell L, Pardi R, Bender J. Induction of transporter associated with antigen processing by interferon γ confers endothelial cell cytoprotection against natural killer-mediated lysis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 2435-2440. PMID: 9482903, PMCID: PMC19366, DOI: 10.1073/pnas.95.5.2435.Peer-Reviewed Original ResearchConceptsMHC IInduction of transportersEndothelial cellsNK-resistant cell linesNatural killer-mediated lysisMajor histocompatibility complex INK inhibitory receptorsNK effector cellsPretreatment of ECB-lymphoblastoid cell linesEC sensitivityDermal microvascular endothelial cellsMicrovascular endothelial cellsCell linesHuman umbilical vein endothelial cellsExpression/functionUmbilical vein endothelial cellsAdenoviral-mediated transductionVascular vulnerabilityVein endothelial cellsNK assaysEffector cellsEndothelial activationInhibitory receptorsDeficient targets
1997
17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization.
Caulin-Glaser T, García-Cardeña G, Sarrel P, Sessa W, Bender J. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circulation Research 1997, 81: 885-92. PMID: 9351464, DOI: 10.1161/01.res.81.5.885.Peer-Reviewed Original ResearchConceptsHuman umbilical vein endothelial cellsEstrogen receptorCytosolic Ca2ENOS activityBasal nitric oxide releaseEndothelial NO synthase activityCardiovascular protective roleNO synthase activityDevelopment of atherosclerosisFemale human umbilical vein endothelial cellsNitric oxide releaseCritical effector moleculeUmbilical vein endothelial cellsVein endothelial cellsCardiovascular protectionEstradiol exposureAnimal modelsCGMP formationProtective roleOxide releaseEndothelial cellsNO releaseE2Physiological concentrationsEffector moleculesCytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines
Blum M, Toninelli E, Anderson J, Balda M, Zhou J, O'Donnell L, Pardi R, Bender J. Cytoskeletal rearrangement mediates human microvascular endothelial tight junction modulation by cytokines. American Journal Of Physiology 1997, 273: h286-h294. PMID: 9249502, DOI: 10.1152/ajpheart.1997.273.1.h286.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthineActinsBucladesineCells, CulturedCytokinesCytoskeletonElectrophysiologyEndothelium, VascularHumansInfant, NewbornInterferon-gammaMaleMembrane PotentialsMembrane ProteinsMicrocirculationPhosphoproteinsSkinTight JunctionsTumor Necrosis Factor-alphaUmbilical VeinsZonula Occludens-1 ProteinConceptsTransmonolayer electrical resistanceSpecialized intercellular structuresTight junctionsF-actin cytoskeletonLarge vessel ECActin cytoskeletonEndothelial cell typesMicrovascular endothelial cellsCytoskeletal rearrangementsStriking fragmentationF-actinProtein distributionCytochalasin DCell typesIntercellular structuresBarrier regulationCytoskeletal alterationsConfocal microscopyMVEC monolayersZO-1Macromolecular fluxCentral roleEC permeabilityEndothelial cellsPrimary cultures
1996
Tumor necrosis factor alpha-induced vascular leakage involves PECAM1 phosphorylation.
Ferrero E, Villa A, Ferrero M, Toninelli E, Bender J, Pardi R, Zocchi M. Tumor necrosis factor alpha-induced vascular leakage involves PECAM1 phosphorylation. Cancer Research 1996, 56: 3211-5. PMID: 8764109.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAntigens, Differentiation, MyelomonocyticBenzoquinonesCapillary PermeabilityCell Adhesion MoleculesCell CompartmentationCells, CulturedEndothelium, VascularEnzyme InhibitorsFluorescent Antibody Technique, IndirectGene ExpressionHumansLactams, MacrocyclicPhosphorylationPlatelet Endothelial Cell Adhesion Molecule-1Protein Kinase InhibitorsQuinonesRifabutinRNA, MessengerStaurosporineTumor Necrosis Factor-alphaUmbilical VeinsConceptsVascular leakageEndothelial cellsNecrosis factor alphaTyrosine kinase inhibitorsHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsNatural tyrosine kinase inhibitorSerine-threonine kinaseVein endothelial cellsSurface redistributionFactor alphaVascular permeabilityVivo administrationKinase inhibitorsCytoskeletal associationMouse liverLavendustin AUse of inhibitorsPhosphorylationInhibitors