2022
mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice
He C, Jiang B, Wang M, Ren P, Murtada SI, Caulk AW, Li G, Qin L, Assi R, Lovoulos CJ, Schwartz MA, Humphrey JD, Tellides G. mTOR inhibition prevents angiotensin II–induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice. JCI Insight 2022, 7: e155815. PMID: 35132962, PMCID: PMC8855820, DOI: 10.1172/jci.insight.155815.Peer-Reviewed Original ResearchConceptsApoE-deficient miceAngiotensin IIVascular wall cellsAortic tearAortic ruptureMTOR inhibitionSmooth muscle cell hypertrophyMatricellular proteinWall cellsSuprarenal abdominal aortaMuscle cell hypertrophyExtracellular matrix accumulationInhibition of mTORRole of mTORSubadventitial hematomaFree ruptureAortic dissectionAortic diseaseAortic aneurysmSignificant dissectionAbdominal aortaHemorrhagic lesionsExtensive dissectionMetalloproteinase expressionCell hypertrophy
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
MicroRNA-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 substratesARHGAP18: 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 abilityTranslocating transcription factors in fluid shear stress-mediated vascular remodeling and disease
Min E, Schwartz MA. Translocating transcription factors in fluid shear stress-mediated vascular remodeling and disease. Experimental Cell Research 2019, 376: 92-97. PMID: 30633880, PMCID: PMC8211025, DOI: 10.1016/j.yexcr.2019.01.005.Peer-Reviewed Original Research
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
2014
Up-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
2010
Integrins and Extracellular Matrix in Mechanotransduction
Schwartz MA. Integrins and Extracellular Matrix in Mechanotransduction. Cold Spring Harbor Perspectives In Biology 2010, 2: a005066. PMID: 21084386, PMCID: PMC2982167, DOI: 10.1101/cshperspect.a005066.Peer-Reviewed Original ResearchMeSH KeywordsCell-Matrix JunctionsCytoskeletonEnvironmentExtracellular MatrixGene Expression RegulationIntegrinsMechanotransduction, CellularModels, BiologicalSignal TransductionConceptsIntegrin-mediated adhesionExtracellular matrixCytoskeletal linker proteinExtracellular matrix fibrilsIntracellular actin filamentsLinker proteinGenetic programActin filamentsExtracellular structuresCell survivalMatrix fibrilsIntegrinsCell functionCurrent knowledgeMechanotransductionMechanical forcesTransmits forcesIntracellularAdhesionCellsCytoskeletonProteinRegulationPathwayEnvironmental forces
2005
The 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
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