2021
TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy
Ostriker AC, Xie Y, Chakraborty R, Sizer AJ, Bai Y, Ding M, Song WL, Huttner A, Hwa J, Martin KA. TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy. Circulation 2021, 144: 455-470. PMID: 34111946, PMCID: PMC8643133, DOI: 10.1161/circulationaha.120.050553.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsApoptosisBiomarkersDioxygenasesDisease Models, AnimalDisease SusceptibilityDNA-Binding ProteinsHeart TransplantationHumansImmunohistochemistryInterferon-gammaMiceMice, KnockoutMyocytes, Smooth MuscleSignal TransductionSTAT1 Transcription FactorTunica IntimaVascular DiseasesConceptsCoronary allograft vasculopathyGraft arteriopathyIntimal thickeningCAV progressionRole of TET2VSMC apoptosisTransplant samplesGraft modelHigh-dose ascorbic acidTET2 expressionVSMC phenotypeContext of transplantCoronary blood flowEffect of IFNγTET2 activityTET2 depletionSmooth muscle cell apoptosisVascular smooth muscle cell apoptosisMuscle cell apoptosisAllograft vasculopathyDevastating sequelaeMedial thinningAortic graftHeart transplantTransplant failure
2020
Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation
Zeng Z, Xia L, Fan S, Zheng J, Qin J, Fan X, Liu Y, Tao J, Liu Y, Li K, Ling Z, Bu Y, Martin KA, Hwa J, Liu R, Tang WH. Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation. Circulation 2020, 143: 354-371. PMID: 33207953, DOI: 10.1161/circulationaha.120.049715.Peer-Reviewed Original ResearchConceptsHuman coronary artery smooth muscle cellsTet2 knockout miceCoronary artery smooth muscle cellsArtery smooth muscle cellsCircular RNAsSmooth muscle cellsVascular smooth muscle cellsWire-injured mouse femoral arteriesSmooth muscle cell differentiationCircular RNA profilingMuscle cell differentiationRNA sequencing dataLoss of TET2Coronary heart diseaseVascular SMC differentiationMiR-22-3pPlatelet-derived growth factorKnockout miceSMC differentiationMaster regulatorRNA sequencingRNA profilingPlatelet-derived growth factor-BBGene expressionSequencing data
2019
LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis
Xie Y, Ostriker AC, Jin Y, Hu H, Sizer AJ, Peng G, Morris AH, Ryu C, Herzog EL, Kyriakides T, Zhao H, Dardik A, Yu J, Hwa J, Martin KA. LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis. Circulation 2019, 139: 679-693. PMID: 30586711, PMCID: PMC6371979, DOI: 10.1161/circulationaha.118.034615.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedDisease Models, AnimalExtracellular MatrixFeedback, PhysiologicalFibrosisHyperplasiaIntegrin alphaVbeta3LIM Domain ProteinsMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaSignal TransductionTranscription Factor AP-1Transcription FactorsTransforming Growth Factor beta1Vascular RemodelingVascular System InjuriesConceptsSmooth muscle cellsActivator protein-1 (AP-1) transcription factorExtracellular matrixProtein-1 transcription factorTransforming Growth Factor β SignalingGrowth factor β signalingMouse smooth muscle cellsTGF-β1 target genesHuman smooth muscle cellsActivator protein-1Muscle-specific deletionNegative feedback regulatorTGF-β pathwayECM protein expressionSmad3 phosphorylationNegative feedback regulationTranscription factorsArteriovenous fistulaECM depositionDomain interactsTGF-β proteinTarget genesLMO7TGF-β treatmentGrowth factor β
2017
Opposing Actions of AKT (Protein Kinase B) Isoforms in Vascular Smooth Muscle Injury and Therapeutic Response
Jin Y, Xie Y, Ostriker AC, Zhang X, Liu R, Lee MY, Leslie KL, Tang W, Du J, Lee SH, Wang Y, Sessa WC, Hwa J, Yu J, Martin KA. Opposing Actions of AKT (Protein Kinase B) Isoforms in Vascular Smooth Muscle Injury and Therapeutic Response. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 2311-2321. PMID: 29025710, PMCID: PMC5699966, DOI: 10.1161/atvbaha.117.310053.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell Cycle ProteinsCell DifferentiationCell MovementCell ProliferationCells, CulturedDisease Models, AnimalForkhead Transcription FactorsGene Expression RegulationGenetic Predisposition to DiseaseHumansMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaNuclear ProteinsPhenotypePromoter Regions, GeneticProto-Oncogene Proteins c-aktRNA InterferenceRNA, MessengerSignal TransductionSirolimusTime FactorsTrans-ActivatorsTranscription FactorsTransfectionVascular System InjuriesConceptsIntimal hyperplasiaTherapeutic inhibitionVascular smooth muscle injurySmooth muscle-specific deletionSmooth muscle cell proliferationSystemic vascular diseaseSevere intimal hyperplasiaSmooth muscle injuryNew treatment strategiesWild-type miceAkt isoformsMuscle cell proliferationMuscle-specific deletionMechanism of actionVascular smooth muscle cell differentiationCoronary revascularizationSmooth muscle cell differentiationDiabetes mellitusDiabetic patientsControl miceRapamycin therapyVascular diseaseMuscle injuryTherapeutic responseSevere thrombosis
2015
Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition
Xie Y, Jin Y, Merenick BL, Ding M, Fetalvero KM, Wagner RJ, Mai A, Gleim S, Tucker DF, Birnbaum MJ, Ballif BA, Luciano AK, Sessa WC, Rzucidlo EM, Powell RJ, Hou L, Zhao H, Hwa J, Yu J, Martin KA. Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition. Science Signaling 2015, 8: ra44. PMID: 25969542, PMCID: PMC4560350, DOI: 10.1126/scisignal.2005482.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationGATA6 Transcription FactorHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultiprotein ComplexesMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesConceptsGATA-6Vascular smooth muscle cell differentiationSmooth muscle cell differentiationPhosphorylation-deficient mutantDifferentiation of VSMCsRapamycin complex 1Downstream transcriptional targetsTranscription factor GATA-6Muscle cell differentiationInhibition of mTORC1VSMC hyperplasiaTransactivation of promotersTranscriptional targetsVSMC differentiationNuclear accumulationInduced phosphorylationMechanistic targetReversible differentiationCell differentiationCells undergoDrug targetsInhibition of proliferationPhosphorylationWild-type miceMTORC1
2013
Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity
Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA. Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity. Circulation 2013, 128: 2047-2057. PMID: 24077167, PMCID: PMC3899790, DOI: 10.1161/circulationaha.113.002887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCell DifferentiationCells, CulturedDioxygenasesDNA-Binding ProteinsEpigenesis, GeneticHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNuclear ProteinsPromoter Regions, GeneticProto-Oncogene ProteinsTrans-ActivatorsWound HealingConceptsTen-Eleven Translocation-2SMC differentiationTET2 knockdownSmooth muscle cellsGene expressionTranslocation 2Smooth Muscle Cell PlasticityMaster epigenetic regulatorSMC gene expressionContractile gene expressionMuscle cell plasticityDedifferentiated smooth muscle cellsTET2 overexpressionContractile smooth muscle cellsHuman smooth muscle cellsChromatin accessibilityEpigenetic landscapeSMC plasticityChromatin immunoprecipitationEpigenetic regulatorsEpigenetic mechanismsCell plasticityMaster regulatorSMC phenotypeTranscriptional upregulation
2004
Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy
McMullen J, Shioi T, Zhang L, Tarnavski O, Sherwood M, Dorfman A, Longnus S, Pende M, Martin K, Blenis J, Thomas G, Izumo S. Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy. Molecular And Cellular Biology 2004, 24: 6231-6240. PMID: 15226426, PMCID: PMC434247, DOI: 10.1128/mcb.24.14.6231-6240.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAortaCardiomegalyFemaleFetusGene Expression Regulation, DevelopmentalMiceMice, KnockoutMice, TransgenicOrgan SizePhosphatidylinositol 3-KinasesPhysical Conditioning, AnimalReceptor, IGF Type 1Ribosomal Protein S6 Kinases, 90-kDaSignal TransductionSirolimusStress, MechanicalSwimmingConceptsRibosomal S6 kinaseS6 kinaseOverexpression of S6K1PI3K mutantCritical downstream effectorRibosomal proteinsTransgenic miceCardiac hypertrophyDownstream effectorsK mutantS6KsGrowth factor pathwaysGenetic relationshipsPathological stressProtein synthesisCritical effectorS6K1K pathwayIGF1 receptorFactor 1Factor pathwayPhysiological stressInsulin-like growth factor-1Physiological stimuliKinase