2021
MEKK3–TGFβ crosstalk regulates inward arterial remodeling
Deng H, Xu Y, Hu X, Zhuang ZW, Chang Y, Wang Y, Ntokou A, Schwartz MA, Su B, Simons M. MEKK3–TGFβ crosstalk regulates inward arterial remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2112625118. PMID: 34911761, PMCID: PMC8713777, DOI: 10.1073/pnas.2112625118.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene DeletionGene Expression RegulationGenotypeHindlimbHuman Umbilical Vein Endothelial CellsHumansHypertension, PulmonaryIschemiaMAP Kinase Kinase Kinase 1MAP Kinase Kinase Kinase 3MiceReceptors, Transforming Growth Factor betaSelective Estrogen Receptor ModulatorsSignal TransductionTamoxifenTransforming Growth Factor betaVascular RemodelingConceptsArterial remodelingSuch common diseasesEndothelial-specific deletionActivation of TGFβArtery diseaseHyperlipidemic miceSpontaneous hypertensionInward remodelingAccelerated progressionArterial diameterVascular remodelingPathogenic importanceAdult miceKnockout miceVascular circuitPathologic conditionsCommon diseaseMAPK ERK1/2MiceRemodelingHypertensionAtherosclerosisControl of proliferationDiseaseProgression
2019
Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity
Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, Mack M, Schwartz MA, Dela Cruz CS, Palm NW, Jackson R, Flavell RA. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 2019, 573: 69-74. PMID: 31435009, PMCID: PMC6939392, DOI: 10.1038/s41586-019-1485-8.Peer-Reviewed Original ResearchConceptsInnate immune cellsImmune cellsInflammatory responseInnate immune systemCyclical hydrostatic pressurePulmonary inflammationImmune responseImmune systemInnate immunityBacterial infectionsIon channel Piezo1InflammationPhysiological fluctuationsImmunityPhysiological roleLocal microenvironmentCellsPiezo1Direct recognitionResponseAutoinflammationLungInfectionMiceARHGAP18: A Flow‐Responsive Gene That Regulates Endothelial Cell Alignment and Protects Against Atherosclerosis
Lay AJ, Coleman PR, Formaz‐Preston A, Ting KK, Roediger B, Weninger W, Schwartz MA, Vadas MA, Gamble JR. ARHGAP18: A Flow‐Responsive Gene That Regulates Endothelial Cell Alignment and Protects Against Atherosclerosis. Journal Of The American Heart Association 2019, 8: e010057. PMID: 30630384, PMCID: PMC6497359, DOI: 10.1161/jaha.118.010057.Peer-Reviewed Original ResearchConceptsApolipoprotein EHigh-fat diet-induced modelIntercellular adhesion molecule-1Endothelial nitric oxide synthaseHigh-fat dietDevelopment of atherosclerosisNitric oxide synthaseDiet-induced modelAdhesion molecule-1Double mutant miceAortic diseaseAtherosclerosis developmentInflammatory phenotypeOxide synthaseMolecule-1AtherosclerosisEarly onsetProtective genesMiceFlow-responsive genesAtheroprotective regionsEndothelial cell alignmentAdaptive responseAnalysis of ECEC ability
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-4Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*
Bancroft T, Bouaouina M, Roberts S, Lee M, Calderwood DA, Schwartz M, Simons M, Sessa WC, Kyriakides TR. Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*. Journal Of Biological Chemistry 2014, 290: 409-422. PMID: 25389299, PMCID: PMC4281743, DOI: 10.1074/jbc.m114.618421.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementFibroblastsGene Expression RegulationGenetic Complementation TestIntegrin beta1MiceMice, KnockoutNeuropeptidesNitric Oxide Synthase Type IIIPrimary Cell CultureProto-Oncogene Proteins c-aktRac1 GTP-Binding ProteinRNA, Small InterferingSignal TransductionSkinThrombospondinsWound HealingWounds, Nonpenetrating
2008
Integrin Agonists as Adjuvants in Chemotherapy for Melanoma
Schwartz MA, McRoberts K, Coyner M, Andarawewa KL, Frierson HF, Sanders JM, Swenson S, Markland F, Conaway MR, Theodorescu D. Integrin Agonists as Adjuvants in Chemotherapy for Melanoma. Clinical Cancer Research 2008, 14: 6193-6197. PMID: 18829498, DOI: 10.1158/1078-0432.ccr-08-1285.Peer-Reviewed Original ResearchConceptsMelanoma linesExtracellular matrixMetastatic melanomaM21 tumorsTherapeutic responseImmunodeficient miceTumor volumeChemotherapyClonal growth assaysTherapy resistanceTumor growthHuman melanomaChemotherapeutic efficacyMelanomaTumor cellsDrug 1Survival assaysM21 cellsM21 melanomaSmall nestsIntegrin agonistsIntegrin-dependent adhesionTumorsMiceSnake venom
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