2024
Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions
Tanaka K, Chen M, Prendergast A, Zhuang Z, Nasiri A, Joshi D, Hintzen J, Chung M, Kumar A, Mani A, Koleske A, Crawford J, Nicoli S, Schwartz M. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. The EMBO Journal 2024, 43: 3175-3191. PMID: 38886581, PMCID: PMC11294477, DOI: 10.1038/s44318-024-00142-0.Peer-Reviewed Original ResearchLatrophilin-2Affinity purification methodCell-cell junctionsHuman genetic dataPECAM-1SiRNA screenGenetic dataEndothelial cell response to fluid shear stressGA proteinsDownstream eventsEndothelial-specific knockoutG-proteinActivity assayShear stress mechanotransductionPlexin-D1Endothelial signalingJunctional complexesPurification methodVE-cadherinResponse to fluid shear stressVascular developmentGA residuesEndothelial junctionsGPCRsVEGF receptors
2017
VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylation
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-3
2013
Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1
Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1. Current Biology 2013, 23: 1024-1030. PMID: 23684974, PMCID: PMC3676707, DOI: 10.1016/j.cub.2013.04.049.Peer-Reviewed Original ResearchConceptsFluid shear stressVE-cadherinCell-cell junctionsPECAM-1Junctional tensionCytoskeletal remodelingVascular morphogenesisGene expressionComplex consistingCells triggersFlow-dependent vascular remodelingIon channelsFRET measurementsEndothelial cells triggersMechanical tensionNormal vascular functionTension sensorDetectable tensionEC responseStatic cultureJunctional receptorsRemodelingCytoskeletonMorphogenesisVascular remodeling
2012
Lessons from the endothelial junctional mechanosensory complex
Conway D, Schwartz MA. Lessons from the endothelial junctional mechanosensory complex. F1000 Biology Reports 2012, 4: 1. PMID: 22238515, PMCID: PMC3251317, DOI: 10.3410/b4-1.Peer-Reviewed Original Research
2010
Atheroprone 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 cells
2008
Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice
Harry BL, Sanders JM, Feaver RE, Lansey M, Deem TL, Zarbock A, Bruce AC, Pryor AW, Gelfand BD, Blackman BR, Schwartz MA, Ley K. Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2008, 28: 2003-2008. PMID: 18688018, PMCID: PMC2651147, DOI: 10.1161/atvbaha.108.164707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, AbdominalAorta, ThoracicApolipoproteins EAtherosclerosisBone Marrow CellsBone Marrow TransplantationCells, CulturedDietary FatsDisease Models, AnimalDisease ProgressionEndothelial CellsHumansMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPlatelet Endothelial Cell Adhesion Molecule-1Regional Blood FlowRNA InterferenceRNA, Small InterferingStress, MechanicalVascular Cell Adhesion Molecule-1ConceptsEndothelial PECAM-1PECAM-1Aortic archAbdominal aortaNF-kappaBVascular cell adhesion molecule-1 expressionCell adhesion molecule-1 expressionAdhesion molecule-1 expressionCell adhesion molecule-1ApoE-deficient miceAtherosclerotic lesion sizeBone marrow transplantationAtherosclerotic lesion formationMolecule-1 expressionVCAM-1 expressionAdhesion molecule-1Endothelial cell adhesion molecule-1NF-kappaB activityNuclear NF-kappaBDisturbed flowMarrow transplantationMacrophage infiltrationLesser curvatureWestern dietDeficient mice
2006
A mechanosensory complex that mediates the endothelial cell response to fluid shear stress
Tzima E, Irani‐Tehrani M, Kiosses W, Dejana E, Schultz D, Engelhardt B, Cao G, DeLisser H, Schwartz M. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. The FASEB Journal 2006, 20: a1378-a1378. DOI: 10.1096/fasebj.20.5.a1378-c.Peer-Reviewed Original ResearchPECAM-1-null miceDownstream inflammatory genesPECAM-1VE-cadherinDevelopment of atherosclerosisICAM-1 expressionNF-kB activationInitiation of atherosclerosisBlood pressureVascular remodelingHigh-affinity stateInflammatory genesNF-κBCell responsesEndothelial cell responsesNull miceMechanosensory complexIntegrin activationAffinity stateAtherosclerosisVEGFR2Heterologous cellsPathway upstreamActivationSrc family kinases
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 transductionPathwayMice