2025
cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling
Deng H, Rukhlenko O, Joshi D, Hu X, Junk P, Tuliakova A, Kholodenko B, Schwartz M. cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling. Science Advances 2025, 11: eado9970. PMID: 39752487, PMCID: PMC11698091, DOI: 10.1126/sciadv.ado9970.Peer-Reviewed Original ResearchConceptsShear stressCell cycle-dependent kinasesHigh shear stressLow shear stressOscillatory shear stressPhysiological shear stressFluid shear stressCell cycle arrestRegulatory networksTranscriptomic statesResponse to drug treatmentCycle arrestCell cycleEndothelial cell cycleDisease susceptibilityRegulatory mechanismsVessel behaviorCDK2Endothelial cellsIn vitroStressRegulationVascular endothelial cellsRemodelingCells
2024
A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling
Deng H, Zhang J, Wang Y, Joshi D, Pi X, De Val S, Schwartz M. A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling. Nature Cardiovascular Research 2024, 3: 785-798. PMID: 39196179, DOI: 10.1038/s44161-024-00496-y.Peer-Reviewed Original ResearchFluid shear stressVascular remodelingOutward remodelingBone morphogenetic proteinShear stressMouse models of type 1Ischemic diseasesModels of type 1BMP-binding endothelial regulatorBlood flow recoveryType 2 diabetesPhysiological fluid shear stressPotential therapeutic approachBlocking antibodiesMouse modelSmad1/5 activationArterial remodelingTherapeutic approachesType 1Akt activationBlood flowEndothelial regulationSmad1/5Flow recoveryMorphogenetic proteinsEndothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studies
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 ResearchConceptsInflammatory 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
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 proliferationDiseaseProgressionActivation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling
Deng H, Min E, Baeyens N, Coon BG, Hu R, Zhuang ZW, Chen M, Huang B, Afolabi T, Zarkada G, Acheampong A, McEntee K, Eichmann A, Liu F, Su B, Simons M, Schwartz MA. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2105339118. PMID: 34504019, PMCID: PMC8449390, DOI: 10.1073/pnas.2105339118.Peer-Reviewed Original ResearchConceptsLow fluid shear stressFluid shear stressNuclear translocationSmad linker regionTransmembrane protein Neuropilin-1Target gene expressionCyclin-dependent kinasesBone morphogenetic proteinEC-specific deletionSmad2/3 nuclear translocationNuclear localizationHigh fluid shear stressLinker regionMorphogenetic proteinsGene expressionRegulatory mechanismsActivation of Smad2/3Receptor ALK5Smad2/3 phosphorylationTranslocationCell sensingEndothelial cell (EC) sensingPhosphorylationALK5Smad2/3
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