2013
Endothelial Cell Sensing of Flow Direction
Wang C, Baker BM, Chen CS, Schwartz MA. Endothelial Cell Sensing of Flow Direction. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 2130-2136. PMID: 23814115, PMCID: PMC3812824, DOI: 10.1161/atvbaha.113.301826.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsAtherosclerosisCattleCell Culture TechniquesCell ShapeCells, CulturedEndothelial CellsEnzyme ActivationHemodynamicsInflammationMechanotransduction, CellularNF-kappa BNitric OxideNitric Oxide Synthase Type IIIOscillometryPhosphorylationProto-Oncogene Proteins c-aktReactive Oxygen SpeciesRegional Blood FlowStress, MechanicalTime FactorsConceptsEndothelial cellsEndothelial nitric oxide synthaseEndothelial nitric oxide synthase pathwayNitric oxide synthase pathwayNitric oxide synthaseOxide synthase pathwayAtherosclerosis-prone regionsInflammatory activationInflammatory effectsOxide synthaseEndothelial cell responsesCell responsesReactive oxygen productionDisturbed flowNitric oxideNuclear factorSimilar effectsActivationCellsSynthase pathwayInability of cells
2012
A novel in vitro flow system for changing flow direction on endothelial cells
Wang C, Lu H, Schwartz MA. A novel in vitro flow system for changing flow direction on endothelial cells. Journal Of Biomechanics 2012, 45: 1212-1218. PMID: 22386042, PMCID: PMC3327813, DOI: 10.1016/j.jbiomech.2012.01.045.Peer-Reviewed Original Research
2011
JNK2 Promotes Endothelial Cell Alignment under Flow
Hahn C, Wang C, Orr AW, Coon BG, Schwartz MA. JNK2 Promotes Endothelial Cell Alignment under Flow. PLOS ONE 2011, 6: e24338. PMID: 21909388, PMCID: PMC3164210, DOI: 10.1371/journal.pone.0024338.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase c-Jun N-terminal kinaseProtein kinase c-Jun N-terminal kinaseC-Jun N-terminal kinaseActin stress fibersN-terminal kinaseFocal adhesionsBasement membrane proteinsMembrane proteinsLaminar shear stressStress fibersGene expressionJNK activityIntegrin activationJNK2 activationEndothelial cell alignmentJNK activationActivated JNKExtracellular matrixInflammatory gene expressionCell alignmentUnexpected connectionEndothelial cellsActivationPathwayCells
2010
Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 2010, 466: 263-266. PMID: 20613844, PMCID: PMC2901888, DOI: 10.1038/nature09198.Peer-Reviewed Original ResearchConceptsFocal adhesionsFocal adhesion dynamicsMembrane cytoskeletal proteinsAdhesion dynamicsCell adhesion moleculeRegulatory mechanismsSpecific proteinsActin filamentsCell adhesionVinculinProteinMechanical tensionMechanical forcesRegulationPhysical forcesMolecular forcesAdhesionCellsVivoMechanotransductionPhysiologyNew biosensorFilamentsAbilityMigrationMatrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Funk SD, Yurdagul A, Green JM, Jhaveri KA, Schwartz MA, Orr AW. Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells. Circulation Research 2010, 106: 1394-1403. PMID: 20224042, PMCID: PMC2862370, DOI: 10.1161/circresaha.109.210286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsBasement MembraneCattleCdc42 GTP-Binding ProteinCells, CulturedCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationEnzyme ActivatorsHumansIloprostInflammationInflammation MediatorsInjections, IntraperitonealIntegrinsMaleMechanotransduction, CellularMiceMice, Inbred C57BLNF-kappa BP21-Activated KinasesPhosphorylationProtein Kinase InhibitorsPulsatile FlowRac GTP-Binding ProteinsRegional Blood FlowStress, MechanicalTime FactorsTransfectionConceptsInflammatory gene expressionNF-kappaB activationInflammatory signalingEndothelial cellsProstacyclin analogue iloprostBasement membrane proteinsBlood flow patternsPKA-dependent inhibitionInflammatory pathwaysAnalogue iloprostGene expressionKappaB activationNF-kappaB.Subendothelial extracellular matrixNuclear factorPAK activationBasement membrane
2009
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA. The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow. Circulation Research 2009, 104: 995-1003. PMID: 19286608, PMCID: PMC2702158, DOI: 10.1161/circresaha.108.186486.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBasement MembraneCattleCell Culture TechniquesCells, CulturedCollagenDisease Models, AnimalEndothelial CellsEnzyme ActivationExtracellular MatrixFibronectinsHemorheologyInflammationIntegrinsJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesOscillometryP21-Activated KinasesPhosphorylationRegional Blood FlowStress, Mechanical
2008
p21-Activated Kinase Signaling Regulates Oxidant-Dependent NF-&kgr;B Activation by Flow
Orr AW, Hahn C, Blackman BR, Schwartz MA. p21-Activated Kinase Signaling Regulates Oxidant-Dependent NF-&kgr;B Activation by Flow. Circulation Research 2008, 103: 671-679. PMID: 18669917, PMCID: PMC2697905, DOI: 10.1161/circresaha.108.182097.Peer-Reviewed Original ResearchConceptsNF-kappaB activationReactive oxygen speciesProinflammatory transcription factor nuclear factorTranscription factor nuclear factorInflammatory gene expressionNF-kappaB pathwayAbility of ROSP21-activated kinaseDisturbed blood flowBlood flowSensitivity of cellsNuclear factorEndothelial cellsROS productionActivationOxygen speciesCellsDisturbed flowGene expressionCollagen
2007
Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK
Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA. Induction of Vascular Permeability: βPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK. Molecular Biology Of The Cell 2007, 18: 2346-2355. PMID: 17429073, PMCID: PMC1877103, DOI: 10.1091/mbc.e06-07-0584.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCapillary PermeabilityCattleCell Cycle ProteinsCells, CulturedEndothelial CellsEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGuanine Nucleotide Exchange FactorsHumansInflammationLipopolysaccharidesLungMiceP21-Activated KinasesPeptidesProtein Serine-Threonine KinasesRho Guanine Nucleotide Exchange FactorsConceptsP21-activated kinaseMitogen-activated protein kinase kinaseEndothelial cell-cell junctionsExtracellular signal-regulated kinaseCell-cell junctionsProtein kinase kinaseMyosin light chain phosphorylationLight chain phosphorylationSignal-regulated kinaseCell-permeant peptideActivation of ERKKinase kinaseExtracellular signalsPAK functionChain phosphorylationCritical regulatorKinaseCell contractilityCell typesCultured endothelial cellsPhosphorylationMouse lung injury modelMyosin phosphorylationEndothelial cellsGIT1Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis
Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA. Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. Journal Of Cell Biology 2007, 176: 719-727. PMID: 17312022, PMCID: PMC2064028, DOI: 10.1083/jcb.200609008.Peer-Reviewed Original ResearchConceptsP21-activated kinaseP21-activated kinase activationAtherosclerosis-prone regionsCell-cell junctionsBasement membrane proteinsMembrane proteinsPAK phosphorylationActivation of PAKKinase activationPAK activationEndothelial permeabilityFibronectinActivationSubendothelial monocytesVivoKinasePhosphorylationProteinVascular permeabilityAtherogenesisRecruitmentCells
2006
Matrix-specific Suppression of Integrin Activation in Shear Stress Signaling
Orr AW, Ginsberg MH, Shattil SJ, Deckmyn H, Schwartz MA. Matrix-specific Suppression of Integrin Activation in Shear Stress Signaling. Molecular Biology Of The Cell 2006, 17: 4686-4697. PMID: 16928957, PMCID: PMC1635406, DOI: 10.1091/mbc.e06-04-0289.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood VesselsCattleCyclic AMP-Dependent Protein KinasesEndothelial CellsEnzyme ActivationExtracellular MatrixFibroblast Growth Factor 2FibronectinsIntegrin alpha2beta1Integrin alpha5beta1Integrin alphaVbeta3Models, BiologicalPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesProtein Kinase CSignal TransductionStress, MechanicalTalin
2005
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 2005, 437: 426-431. PMID: 16163360, DOI: 10.1038/nature03952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCattleCell AdhesionCells, CulturedEndothelial CellsFemaleGene DeletionMechanotransduction, CellularMiceMice, KnockoutMultiprotein ComplexesNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1RatsStress, MechanicalVascular Endothelial Growth Factor Receptor-2ConceptsDownstream inflammatory genesPECAM-1 knockout miceVascular endothelial cell cadherinVascular remodellingHigh-affinity stateInflammatory genesNF-κBVascular homeostasisEndothelial cell responsesCell responsesMechanosensory complexPECAM-1Heterologous cellsPathway upstreamCardiac developmentIntegrin activationAtherogenesisMechanism of transductionPathwayMiceThe subendothelial extracellular matrix modulates NF-κB activation by flow
Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA. The subendothelial extracellular matrix modulates NF-κB activation by flow. Journal Of Cell Biology 2005, 169: 191-202. PMID: 15809308, PMCID: PMC2171897, DOI: 10.1083/jcb.200410073.Peer-Reviewed Original ResearchConceptsNF-kappaB activationSubendothelial extracellular matrixAtherosclerosis-prone sitesEarly monocyte recruitmentSigns of atherosclerosisFatty streak formationNovel therapeutic strategiesNF-κB activationSuppress NF-kappaB activationExtracellular matrixMonocyte recruitmentICAM-1VCAM-1Plaque formTherapeutic strategiesE-selectinP38-dependent pathwayNF-kappaBEndothelial cellsAtherosclerosisP38 activationNew integrinActivationStreak formationIntegrin alpha2beta1
2004
VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*
Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function*. Journal Of Biological Chemistry 2004, 280: 2405-2408. PMID: 15579907, DOI: 10.1074/jbc.c400431200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAngiogenesis InhibitorsAnimalsAntigens, CDAortaBlotting, WesternCadherinsCattleCell MovementCells, CulturedCytokinesEndothelium, VascularEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGap JunctionsGreen Fluorescent ProteinsImmunoprecipitationMicroscopy, ConfocalMicroscopy, FluorescenceNeovascularization, PathologicProtein BindingRecombinant ProteinsSignal TransductionTryptophan-tRNA LigaseVascular Endothelial Growth Factor AConceptsT2-TrpRSp21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*
Stockton RA, Schaefer E, Schwartz MA. p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*. Journal Of Biological Chemistry 2004, 279: 46621-46630. PMID: 15333633, DOI: 10.1074/jbc.m408877200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, WesternCattleCell CommunicationCells, CulturedCytokinesCytoskeletonEndothelium, VascularEnzyme ActivationHumansInflammationIschemiaMicroscopy, FluorescenceMuscle ContractionMyosin Light ChainsP21-Activated KinasesPeptidesPhosphorylationProtein Serine-Threonine KinasesProtein TransportThrombinTime FactorsTransfectionUmbilical VeinsConceptsP21-activated kinaseClose cell-cell associationsEndothelial cell-cell junctionsCell-cell junctionsActin stress fibersCell-cell associationsSuitable drug targetsGrowth factorMyosin phosphorylationHuman umbilical vein endothelial cellsCentral regulatorStress fibersUmbilical vein endothelial cellsEndothelial cellsPAK activationDrug targetsVein endothelial cellsCell contractilityMultiple growth factorsParacellular poresEndothelial permeabilityPhosphorylationPathological processesPathological conditionsPotential roleRho Mediates the Shear-Enhancement of Endothelial Cell Migration and Traction Force Generation
Shiu YT, Li S, Marganski WA, Usami S, Schwartz MA, Wang YL, Dembo M, Chien S. Rho Mediates the Shear-Enhancement of Endothelial Cell Migration and Traction Force Generation. Biophysical Journal 2004, 86: 2558-2565. PMID: 15041692, PMCID: PMC1304103, DOI: 10.1016/s0006-3495(04)74311-8.Peer-Reviewed Original Research
2003
Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells
Tzima E, Reader J, Irani-Tehrani M, Ewalt K, Schwartz M, Schimmel P. Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 14903-14907. PMID: 14630953, PMCID: PMC299850, DOI: 10.1073/pnas.2436330100.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAnimalsCattleCytoskeletonEndothelium, VascularGenetic VectorsHumansLuciferasesMicroscopy, FluorescenceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeovascularization, PathologicNitric Oxide SynthaseProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionStress, MechanicalTemperatureTime FactorsTranscription, GeneticConceptsT2-TrpRSStress-responsive gene expressionHuman tryptophanyl-tRNA synthetaseStress-responsive genesExtracellular signal-regulated kinase 1/2Growth factor stimulationHuman tRNA SynthetaseSignal-regulated kinase 1/2Natural splice variantProtein kinase BShear stress-responsive genesVascular endothelial growth factor (VEGF) stimulationTryptophanyl-tRNA synthetaseVascular homeostasisGrowth factor-induced angiogenesisVascular endothelial growth factor-induced angiogenesisCytoskeletal reorganizationProtein kinaseFactor stimulationAngiogenesis-related activitiesGene expressionKinase BKinase 1/2TRNA synthetaseEndothelial cell responsesRho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins
Lin T, Zeng L, Liu Y, DeFea K, Schwartz MA, Chien S, Shyy J. Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins. Circulation Research 2003, 92: 1296-1304. PMID: 12775580, DOI: 10.1161/01.res.0000078780.65824.8b.Peer-Reviewed Original ResearchMeSH KeywordsActin Depolymerizing FactorsActinsAnimalsCattleCCAAT-Enhancer-Binding ProteinsCell AdhesionCells, CulturedCHO CellsCricetinaeDNA-Binding ProteinsEndothelium, VascularHumansIntracellular Signaling Peptides and ProteinsLim KinasesLuciferasesMembrane ProteinsMicrofilament ProteinsMicroscopy, FluorescenceMutationPlasmidsProtein KinasesProtein Serine-Threonine KinasesProtein TransportProteinsRho GTP-Binding ProteinsRho-Associated KinasesSignal TransductionSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Stress, MechanicalTranscription FactorsTransfectionConceptsSterol regulatory element-binding proteinLIMK-cofilin pathwayRegulatory element-binding proteinLIM kinaseElement-binding proteinRho-ROCKBinding proteinFluid shear stressSREBP cleavage-activating proteinSignal transduction pathwaysSmall GTPase RhoStress activationShear stress activationGolgi transportS2P proteasesTransduction pathwaysNegative mutantGTPase RhoSREBP activationIntegrin activationEndoplasmic reticulumEndothelial cell functionVascular endothelial cellsCaspase-3ProteinLocalized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress*
Tzima E, Kiosses WB, del Pozo MA, Schwartz MA. Localized Cdc42 Activation, Detected Using a Novel Assay, Mediates Microtubule Organizing Center Positioning in Endothelial Cells in Response to Fluid Shear Stress*. Journal Of Biological Chemistry 2003, 278: 31020-31023. PMID: 12754216, DOI: 10.1074/jbc.m301179200.Peer-Reviewed Original ResearchConceptsMicrotubule organizing centerCdc42 activityCdc42 activationFluid shear stressSmall GTPase Cdc42Protein kinase CzetaGTPase Cdc42Early embryosEndothelial cellsIntegrin dynamicsOrganizing centerCdc42Extracellular matrixLocalized activationFluorescence energy transferMTOC localizationVascular endothelial cellsSingle cellsNovel assayCellsActivationPar6CzetaGolgiEmbryos
2002
Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression
Tzima E, Del Pozo MA, Kiosses WB, Mohamed SA, Li S, Chien S, Schwartz MA. Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. The EMBO Journal 2002, 21: 6791-6800. PMID: 12486000, PMCID: PMC139108, DOI: 10.1093/emboj/cdf688.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCell AdhesionCells, CulturedCytoskeletonDimerizationEnergy TransferEnzyme ActivationGene Expression RegulationGenes, DominantGreen Fluorescent ProteinsGTP PhosphohydrolasesIntercellular Adhesion Molecule-1LeukocytesLuciferasesLuminescent ProteinsMicroscopy, FluorescenceNF-kappa BPlasmidsProtein TransportRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSpectrometry, FluorescenceStress, MechanicalTime FactorsTransfectionConceptsGene expressionFluorescence resonance energy transferSmall GTPase RacActivation of Rac1Endothelial cellsFocal adhesionsCytoskeletal organizationCytoskeletal reorganizationGTPase RacRac1 activationAdhesion receptorsResonance energy transferExtracellular matrixNuclear factor-kappaBNew integrinRac1Hemodynamic shear stressSubsequent expressionFactor-kappaBCell alignmentExpressionUnifying modelHemodynamic forcesCell adhesion molecule-1Cells
2001
Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment
Tzima E, del Pozo M, Shattil S, Chien S, Schwartz M. Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment. The EMBO Journal 2001, 20: 4639-4647. PMID: 11532928, PMCID: PMC125600, DOI: 10.1093/emboj/20.17.4639.Peer-Reviewed Original ResearchAnimalsAortaCattleCells, CulturedCulture Media, Serum-FreeCytoskeletonEndothelium, VascularExtracellular Matrix ProteinsFibronectinsGreen Fluorescent ProteinsIntegrinsKineticsLuminescent ProteinsProtein ConformationReceptors, VitronectinRecombinant ProteinsRho GTP-Binding ProteinsStress, MechanicalTime FactorsTransfection