2024
A Concept of “Athero-Oncology”: Tumor-Like Smooth Muscle Cells Drive Atherosclerosis
Chatterjee P, Martin K. A Concept of “Athero-Oncology”: Tumor-Like Smooth Muscle Cells Drive Atherosclerosis. Circulation 2024, 149: 1899-1902. PMID: 38857330, DOI: 10.1161/circulationaha.124.069446.Peer-Reviewed Original Research
2019
Promoters to Study Vascular Smooth Muscle
Chakraborty R, Saddouk FZ, Carrao AC, Krause DS, Greif DM, Martin KA. Promoters to Study Vascular Smooth Muscle. Arteriosclerosis Thrombosis And Vascular Biology 2019, 39: 603-612. PMID: 30727757, PMCID: PMC6527360, DOI: 10.1161/atvbaha.119.312449.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell LineCell LineageCell TransdifferentiationGene Expression RegulationGene Knockout TechniquesGene TargetingHumansMiceMicrofilament ProteinsMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleMyofibroblastsMyosin Heavy ChainsNeovascularization, PathologicNeovascularization, PhysiologicPhenotypePromoter Regions, GeneticRecombinant Fusion ProteinsConceptsSmooth muscle cellsCre driver linesDiversity of phenotypesMuscle cell typesVisceral smooth muscle cellsSMC transdifferentiationActa2 promoterRemarkable plasticityExciting new eraSMC functionCell typesCre linesEmbryonic heartExciting discoveriesPhenotypeMuscle cellsPerivascular adipocytesPromoterVascular smooth muscleNonmuscular cellsExpressionMyeloid cellsCardiovascular phenotypesCellsBlood vessel wallLMO7 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
2018
TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia
Srivastava R, Rolyan H, Xie Y, Li N, Bhat N, Hong L, Esteghamat F, Adeniran A, Geirsson A, Zhang J, Ge G, Nobrega M, Martin KA, Mani A. TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia. Arteriosclerosis Thrombosis And Vascular Biology 2018, 39: 250-262. PMID: 30567484, PMCID: PMC6365015, DOI: 10.1161/atvbaha.118.311830.Peer-Reviewed Original ResearchConceptsInjury-induced intimal hyperplasiaIntimal hyperplasiaObstructive coronary artery diseaseVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationVascular Smooth Muscle Cell PlasticityLRP6 mutant miceOverexpression of TCF7L2Coronary artery diseaseVascular smooth muscle cellsMultiple mouse modelsMuscle cell dedifferentiationWild-type littermatesSmooth muscle cellsRole of TCF7L2Smooth Muscle Cell PlasticityVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationArtery diseaseSM-MHCMouse modelCell cycle inhibitorsHaploinsufficient miceHyperplasia
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
2007
Regulation of vascular smooth muscle cell differentiation
Rzucidlo E, Martin K, Powell R. Regulation of vascular smooth muscle cell differentiation. Journal Of Vascular Surgery 2007, 45: a25-a32. PMID: 17544021, DOI: 10.1016/j.jvs.2007.03.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsVascular smooth muscle cell differentiationSmooth muscle cell differentiationMuscle cell differentiationCell differentiationPathogenesis of atherosclerosisMajor human diseasesLocal environmental cuesEnvironmental cuesContractile roleIntimal hyperplasiaDifferentiated stateVascular aneurysmsMolecular mechanismsVascular developmentPhenotypic switchingHuman diseasesVessel wallVSMCCritical roleDifferentiationEssential componentHypertensionAsthmaAtherosclerosisHyperplasia
2005
Endothelial cell activation of the smooth muscle cell phosphoinositide 3-kinase/Akt pathway promotes differentiation
Brown D, Rzucidlo E, Merenick B, Wagner R, Martin K, Powell R. Endothelial cell activation of the smooth muscle cell phosphoinositide 3-kinase/Akt pathway promotes differentiation. Journal Of Vascular Surgery 2005, 41: 509-516. PMID: 15838487, DOI: 10.1016/j.jvs.2004.12.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicCattleCell DifferentiationCells, CulturedCoculture TechniquesEndothelial CellsMuscle, Smooth, VascularMyocytes, Smooth MusclePhenotypePhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionConceptsEC/SMCDifferentiated SMC phenotypeSMC phenotypeSMC differentiationSmooth muscle cellsAkt pathwayProtein markersProtein kinase AktAdenoviral overexpressionContractile protein markersDominant-negative AktEndothelial cellsOpposite endothelial cellsBlood vessel developmentRapid Akt phosphorylationPI3K/Akt pathwayMuscle cellsWestern blottingKinase AktAbility of ECsActive AktPhosphoinositide 3Kinase activityMolecular signalsSynthetic phenotype
2003
The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation
Martin K, Rzucidlo E, Merenick B, Fingar D, Brown D, Wagner R, Powell R. The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation. American Journal Of Physiology - Cell Physiology 2003, 286: c507-c517. PMID: 14592809, DOI: 10.1152/ajpcell.00201.2003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicBiomarkersCattleCell Cycle ProteinsCell DifferentiationCells, CulturedCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent Kinase Inhibitor p27CyclinsEndothelium, VascularExtracellular Matrix ProteinsImmunosuppressive AgentsMuscle ContractionMuscle, Smooth, VascularPhenotypeProtein KinasesRibosomal Protein S6 Kinases, 70-kDaSignal TransductionSirolimusTOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsVascular smooth muscle cellsVSMC differentiationVascular smooth muscle cell differentiationSmooth muscle cell differentiationVSMC gene expressionRapamycin-sensitive mTORMuscle cell differentiationContractile morphologyCyclin-dependent kinase inhibitorCell cycle withdrawalExtracellular matrix protein synthesisContractile proteinsMTOR pathway inhibitor rapamycinMuscle alpha-actinTranscriptional controlMatrix protein synthesisNovel functionGene expressionMigratory phenotypeRapamycin inductionMultiple speciesCell differentiationInhibitor rapamycinS6K1 pathwayProtein synthesis
1997
Angiotensin II activates the beta 1 isoform of phospholipase C in vascular smooth muscle cells
Schelling J, Nkemere N, Konieczkowski M, Martin K, Dubyak G. Angiotensin II activates the beta 1 isoform of phospholipase C in vascular smooth muscle cells. American Journal Of Physiology 1997, 272: c1558-c1566. PMID: 9176147, DOI: 10.1152/ajpcell.1997.272.5.c1558.Peer-Reviewed Original ResearchConceptsAortic vascular smooth muscle cellsVascular smooth muscle cellsHuman aortic vascular smooth muscle cellsPLC-beta 1Ang IISmooth muscle cellsPLC beta isoformsPLC-beta 1 antibodyRat aortic vascular smooth muscle cellsPermeabilized vascular smooth muscle cellsMuscle cellsGrowth factorPathophysiology of hypertensionAngiotensin II receptorsIP formationReverse transcriptase-polymerase chain reactionPLC-gamma 1 antibodyTranscriptase-polymerase chain reactionPlatelet-derived growth factorCytosolic free Ca2Gamma 1 antibodiesAng II signalsAngiotensin IIAlpha antibodyII receptors