2022
High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells
Deng H, Schwartz MA. High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells. Journal Of The American Heart Association 2022, 11: e025337. PMID: 35861829, PMCID: PMC9707828, DOI: 10.1161/jaha.121.025337.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelial CellsEpithelial-Mesenchymal TransitionMiceSignal TransductionStress, MechanicalConceptsInflammatory cytokinesSmad2/3 activationEndothelial cellsNuclear translocationInflammatory cytokine treatmentGrowth factor betaVascular endothelial cellsQuantitative polymerase chain reactionSmad2/3 nuclear translocationTarget gene expressionBackground AtherosclerosisInflammatory mediatorsInflammatory pathwaysPolymerase chain reactionResult of inhibitionCytokine treatmentInhibits CytokineFactor betaMesenchymal transitionHigh fluid shear stressCytokinesEndMTGene expressionLaminar fluid shear stressFluid shear stress
2019
Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation
Ramírez CM, Zhang X, Bandyopadhyay C, Rotllan N, Sugiyama MG, Aryal B, Liu X, He S, Kraehling JR, Ulrich V, Lin CS, Velazquez H, Lasunción MA, Li G, Suárez Y, Tellides G, Swirski FK, Lee WL, Schwartz MA, Sessa WC, Fernández-Hernando C. Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation. Circulation 2019, 140: 225-239. PMID: 31154825, PMCID: PMC6778687, DOI: 10.1161/circulationaha.118.038571.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseDiet-induced atherosclerosisNO productionVascular inflammationENOS activationEndothelial nitric oxide synthase activationNitric oxide synthase activationAthero-protective functionsLipid metabolic factorsEndothelial cell inflammationNitric oxide synthaseWild-type miceMice Lacking ExpressionProduction of NOExtracellular matrix remodelingInflammatory primingHyperlipidemic miceInflammatory pathwaysAortic archCell inflammationOxide synthaseMetabolic factorsMouse modelAtherosclerosisInflammationMicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis
Moro A, Driscoll TP, Boraas LC, Armero W, Kasper DM, Baeyens N, Jouy C, Mallikarjun V, Swift J, Ahn SJ, Lee D, Zhang J, Gu M, Gerstein M, Schwartz M, Nicoli S. MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis. Nature Cell Biology 2019, 21: 348-358. PMID: 30742093, PMCID: PMC6528464, DOI: 10.1038/s41556-019-0272-y.Peer-Reviewed Original ResearchConceptsArgonaute 2MicroRNA-dependent regulationMechanical homeostasisMicroRNA recognition elementsExtracellular matrix proteinsZebrafish finsMicroRNA familiesTarget mRNAsVertebrate tissuesHyper-contractile phenotypesRegulatory pathwaysUntranslated regionRecognition elementMatrix proteinsComprehensive identificationCaM mRNAConnective tissue growth factorExtracellular matrix depositionHomeostasisTissue growth factorMRNAFibroblast cellsMicroRNAsGrowth factorSoft substrates
2018
Vinculin and the mechanical response of adherent fibroblasts to matrix deformation
Rosowski KA, Boltyanskiy R, Xiang Y, Van den Dries K, Schwartz MA, Dufresne ER. Vinculin and the mechanical response of adherent fibroblasts to matrix deformation. Scientific Reports 2018, 8: 17967. PMID: 30568231, PMCID: PMC6299284, DOI: 10.1038/s41598-018-36272-9.Peer-Reviewed Original ResearchConceptsFocal adhesion protein vinculinAdhesion protein vinculinExtracellular matrix stiffnessIntegrin-mediated adhesionTraction forceProtein vinculinMechanical cuesCellular forcesMatrix stiffnessAdherent fibroblastsECM deformationMouse fibroblastsTraction stressMatrix deformationMechanical responseVinculinMechanical energyApparent stiffnessDeformationFibroblastsStiffnessCellsStretchForceExpressionLocal Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale
Kumar A, Anderson KL, Swift MF, Hanein D, Volkmann N, Schwartz MA. Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale. Biophysical Journal 2018, 115: 1569-1579. PMID: 30274833, PMCID: PMC6372196, DOI: 10.1016/j.bpj.2018.08.045.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCells, CulturedCytoskeletonFocal AdhesionsMechanotransduction, CellularMiceMice, KnockoutTalinConceptsActin organizationLocal actin organizationTalin tension sensorFocal adhesion dynamicsLinear actin filamentsIndividual focal adhesionsCellular force transmissionF-actin alignmentFocal adhesionsAdhesion dynamicsCell centerVinculin localizationActin intensityActin filamentsF-actinAdhesion centersNormal physiologyTalinSame cellsAdhesion correlatesStable adhesionTension sensorDistinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy
Liao X, Shen Y, Zhang R, Sugi K, Vasudevan NT, Alaiti MA, Sweet DR, Zhou L, Qing Y, Gerson SL, Fu C, Wynshaw-Boris A, Hu R, Schwartz MA, Fujioka H, Richardson B, Cameron MJ, Hayashi H, Stamler JS, Jain MK. Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e4661-e4669. PMID: 29712858, PMCID: PMC5960298, DOI: 10.1073/pnas.1720065115.Peer-Reviewed Original ResearchConceptsNonischemic cardiomyopathyKruppel-like factor 4Resident macrophage proliferationNonresident macrophagesHeart failureCardiac functionMyeloid cellsBlood-borne macrophagesPreserves cardiac functionMacrophage proliferationPressure overload hypertrophyValvular diseaseOverload hypertrophyMyocardial angiogenesisAdaptive responseFirst weekMajor causeAngiogenic activityGenetic mutationsMacrophagesFactor 4CardiomyopathyKey transcription factorProliferationDistinct roles
2017
Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification
Fang JS, Coon BG, Gillis N, Chen Z, Qiu J, Chittenden TW, Burt JM, Schwartz MA, Hirschi KK. Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification. Nature Communications 2017, 8: 2149. PMID: 29247167, PMCID: PMC5732288, DOI: 10.1038/s41467-017-01742-7.Peer-Reviewed Original ResearchConceptsEndothelial cell cycle arrestArterial gene expressionCell cycle arrestArterial specificationGene expressionCycle arrestArterial-venous specificationCell cycle inhibitor CDKN1BEndothelial cell cycleCell cycle inhibitionEmbryonic developmentBlood vessel formationP27 axisFunctional vascular networkCell cycleGrowth controlSpecialized phenotypeFluid shear stressCycle inhibitionVessel formationGrowth inhibitionTissue repairMechanochemical pathwayEndothelial cellsVascular regeneration
2016
Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nature Cell Biology 2016, 18: 1043-1053. PMID: 27595237, PMCID: PMC5301150, DOI: 10.1038/ncb3405.Peer-Reviewed Original ResearchConceptsInflammatory signalingIntegrin α5Enhanced phosphodiesterase activityExtracellular matrix remodellingModulates inflammationTherapeutic targetInflammationProstacyclin secretionLipid metabolismEndothelial cellsMatrix remodellingVivo knockdownECM remodellingBasement membraneIntegrin α2Phosphodiesterase activityMolecular mechanismsRemodellingΑ5Direct bindingSignalingCellsFibronectinAtherosclerosisArtery
2015
Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
Coon BG, Baeyens N, Han J, Budatha M, Ross TD, Fang JS, Yun S, Thomas JL, Schwartz MA. Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex. Journal Of Cell Biology 2015, 208: 975-986. PMID: 25800053, PMCID: PMC4384728, DOI: 10.1083/jcb.201408103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCell MovementCells, CulturedEndothelium, VascularHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularMiceMice, Inbred C57BLNeovascularization, PhysiologicPlaque, AtheroscleroticPlatelet Endothelial Cell Adhesion Molecule-1Protein Structure, TertiaryRNA InterferenceRNA, Small InterferingStress, MechanicalStress, PhysiologicalVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation
Tornavaca O, Chia M, Dufton N, Almagro LO, Conway DE, Randi AM, Schwartz MA, Matter K, Balda MS. ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation. Journal Of Cell Biology 2015, 208: 821-838. PMID: 25753039, PMCID: PMC4362456, DOI: 10.1083/jcb.201404140.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAdherens JunctionsAnimalsAntigens, CDCadherinsCapillary PermeabilityCell Adhesion MoleculesCell MovementCells, CulturedClaudin-5Cytoskeletal ProteinsCytoskeletonEndothelial CellsHumansMechanotransduction, CellularMice, Inbred C57BLMyosinsNeovascularization, PhysiologicProtein TransportReceptors, Cell SurfaceTight JunctionsZonula Occludens-1 ProteinConceptsCell-cell tensionAdherens junctionsActive myosin IIZO-1VE-cadherinBarrier formationEndothelial adherens junctionsJunctional recruitmentPrimary endothelial cellsCadherin complexActomyosin organizationCentral regulatorStress fibersInhibition of ROCKMyosin IIProtein ZO-1Tight junction protein ZO-1Cell migrationIntercellular junctionsP114RhoGEFMechanotransducersTight junctionsEndothelial junctionsEndothelial cellsTight junction disruptionRac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction
Daneshjou N, Sieracki N, van Nieuw Amerongen GP, Conway D, Schwartz M, Komarova Y, Malik A. Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction. Journal Of Cell Biology 2015, 208: 23-32. PMID: 25559184, PMCID: PMC4284224, DOI: 10.1083/jcb.201409108.Peer-Reviewed Original ResearchActomyosinAdherens JunctionsAntigens, CDCadherinsCell AdhesionCells, CulturedEndothelial CellsEnzyme ActivationHumansKineticsMicroscopy, FluorescenceMicroscopy, VideoModels, BiologicalMyosin Type IIProtein BindingProtein Kinase InhibitorsProtein MultimerizationProtein StabilityRac1 GTP-Binding ProteinRho-Associated KinasesTime-Lapse ImagingTransfection
2014
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 17308-17313. PMID: 25404299, PMCID: PMC4260558, DOI: 10.1073/pnas.1413725111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlotting, WesternCells, CulturedEndothelial CellsFemaleHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNF-kappa BReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionStress, MechanicalSyndecan-4Vascular Endothelial Growth Factor Receptor-2ConceptsHuman umbilical vein endothelial cellsNF-κBProinflammatory NF-κBAtherosclerotic plaque burdenKruppel-like factor 2Umbilical vein endothelial cellsVEGF receptor 2Appearance of plaquesVein endothelial cellsHypercholesterolemic micePlaque burdenAntiinflammatory pathwayThoracic aortaReceptor 2Endothelial cellsEndothelial alignmentFlow correlatesCausal roleAtherosclerosisFactor 2MiceCyclic stretchLocalization correlatesActivationSyndecan-4
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
The role of p21-activated kinase in the initiation of atherosclerosis
Jhaveri K, Debnath P, Chernoff J, Sanders J, Schwartz M. The role of p21-activated kinase in the initiation of atherosclerosis. BMC Cardiovascular Disorders 2012, 12: 55. PMID: 22824149, PMCID: PMC3489605, DOI: 10.1186/1471-2261-12-55.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesAtherosclerosisBiomechanical PhenomenaCells, CulturedDisease Models, AnimalEndothelial CellsFibronectinsGalectin 3ImmunohistochemistryInflammation MediatorsIntercellular Adhesion Molecule-1MaleMiceMice, Inbred C57BLMice, KnockoutP21-Activated KinasesRegional Blood FlowTranscription Factor RelBVascular Cell Adhesion Molecule-1ConceptsLesser curvatureNF-κB subunitsInflammatory activationEndothelial cellsAtherosclerosis-prone sitesPro-inflammatory functionsInflammatory marker expressionNormal chow dietArch of aortaInitiation of atherosclerosisInflammatory markersOverall inflammationChow dietInflammatory pathwaysYoung miceAtherosclerosis-susceptible regionsConclusionThese dataICAM-1VCAM-1NF-κBRelA NF-κB subunitMarker expressionLow levelsFibronectin depositionInflammationA 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
2010
Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis
Shin ME, He Y, Li D, Na S, Chowdhury F, Poh YC, Collin O, Su P, de Lanerolle P, Schwartz MA, Wang N, Wang F. Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis. Blood 2010, 116: 3297-3310. PMID: 20616216, PMCID: PMC2995358, DOI: 10.1182/blood-2009-12-260851.Peer-Reviewed Original ResearchAtheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation
Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR. Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation. Circulation Research 2010, 106: 1703-1711. PMID: 20378855, PMCID: PMC2891748, DOI: 10.1161/circresaha.109.216283.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedDisease Models, AnimalEndothelium, VascularFeedback, PhysiologicalFibronectinsHemodynamicsHumansInflammationMechanotransduction, CellularMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Pulsatile FlowRegional Blood FlowRNA InterferenceStress, MechanicalTime FactorsTransfectionUp-RegulationConceptsFN depositionAtheroprone flowPECAM-1FN expressionTranscription factor NF-kappaB.Platelet endothelial cell adhesion moleculeNF-kappaB activationNF-kappaB activityAtheroprone hemodynamicsHuman endothelial cellsEndothelial inflammationProinflammatory phenotypeAortic archInduction of fibronectinCarotid arteryCell adhesion moleculeExogenous fibronectinInflammatory signalingFN accumulationNF-kappaBSustained increaseNF-kappaB.Nuclear factorTransient increaseEndothelial cellsMatrix-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
RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling
Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling. Current Biology 2009, 20: 75-79. PMID: 20005108, PMCID: PMC2822103, DOI: 10.1016/j.cub.2009.11.016.Peer-Reviewed Original ResearchConceptsPlasma membraneRecycling endosomesGrowth signalingActivation of Arf6Small GTPase RalACaveolin-dependent internalizationLipid raft microdomainsAnchorage-independent growthEffects of integrinsExocyst complexActive RalARaft microdomainsMembrane raftsRaft markersIntegrin signalingPancreatic cancer cellsRalAAnchorage dependenceAnchorage independenceCell growthSignalingCell detachmentCancer cellsEndosomesExocytosisFocal adhesion kinase modulates activation of NF-κB by flow in endothelial cells
Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells. American Journal Of Physiology - Cell Physiology 2009, 297: c814-c822. PMID: 19587216, PMCID: PMC2770750, DOI: 10.1152/ajpcell.00226.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleusCells, CulturedEndothelial CellsEndothelium, VascularFocal Adhesion Protein-Tyrosine KinasesHydrogen PeroxideI-kappa B KinaseIntegrinsIntercellular Adhesion Molecule-1MiceNF-kappa BPhosphorylationProtein TransportRac GTP-Binding ProteinsReactive Oxygen SpeciesSignal TransductionStress, MechanicalTranscription Factor RelATumor Necrosis Factor-alphaConceptsFocal adhesion kinaseAdhesion kinaseNF-kappaBRac activationTranscriptional activityDependent genesEndothelial cellsIntegrin activationP65 NF-kappaB subunitDegradation of IkappaBReactive oxygen productionFluid shear stressNF-kappaB subunitsSerine 536Phosphorylation of p65Novel mechanismNF-kappaB activationKinaseNF-kappaB phosphorylationPhosphorylationActivationNF-κBOxygen productionHydrogen peroxideCells