2024
Abstract 1147: Crosstalk Between Alk5 And Mtorc1 Signaling Promotes VSMC Differentiation And The Therapeutic Effect Of Rapamycin
Chakraborty R, Chatterjee P, Dave J, Obrien B, Joshi D, Schulz V, Greif D, Hwa J, Gallagher P, Martin K. Abstract 1147: Crosstalk Between Alk5 And Mtorc1 Signaling Promotes VSMC Differentiation And The Therapeutic Effect Of Rapamycin. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a1147-a1147. DOI: 10.1161/atvb.44.suppl_1.1147.Peer-Reviewed Original ResearchVascular smooth muscle cellsTherapeutic effect of rapamycinEffects of rapamycinVSMC differentiationContractile genesConsistent with in vitro findingsRapamycin treatmentCarotid artery injuryHuman coronary artery SMCsVascular smooth muscle cell differentiationIntimal hyperplasiaSmooth muscle cellsCoronary artery SMCsMTORC1 inhibitor rapamycinPhosphorylation of Smad2/3Inhibition of ALK5Smad-binding elementSmad transcription factorsALK5 activityArterial injuryArtery SMCsKnockout miceInhibition of mTORC1Vascular smooth muscle cell plasticityMuscle cells
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
2010
Adiponectin Is Secreted by Vascular Smooth Muscle Cells and Regulates Muscle Contractile Phenotype
Ding M, Wagner R, Martin K. Adiponectin Is Secreted by Vascular Smooth Muscle Cells and Regulates Muscle Contractile Phenotype. The FASEB Journal 2010, 24: 957.5-957.5. DOI: 10.1096/fasebj.24.1_supplement.957.5.Peer-Reviewed Original ResearchAdiponectin overexpressionContractile phenotypeVSMC contractile proteinsVascular smooth muscle cellsSmooth muscle cellsContractile protein expressionVascular smooth muscle cell differentiationVSMC contractile phenotypeCardioprotective adipokineSmooth muscle cell differentiationVisceral fatReceptors AdipoR1Endogenous adiponectinRecombinant adiponectinAdiponectinParacrine actionCardioprotective functionParacrine mannerVSMC proliferationHigher order oligomeric formsSiRNA knock-downMuscle cell differentiationMuscle cellsContractile proteinsVSMC
2009
Adiponectin Induces Vascular Smooth Muscle Cell Differentiation via AMPK
Ding M, Wagner R, Fetalvero K, Kasza Z, Powell R, Martin K. Adiponectin Induces Vascular Smooth Muscle Cell Differentiation via AMPK. The FASEB Journal 2009, 23: 577.10-577.10. DOI: 10.1096/fasebj.23.1_supplement.577.10.Peer-Reviewed Original ResearchMTOR inhibitionLower adiponectin levelsVSMC differentiationType 2 diabetesVascular smooth muscle cell phenotypeSmooth muscle cell phenotypeAMPK activationDose-dependent mannerContractile protein expressionAMPK inhibitor compound C.Muscle cell phenotypeVascular smooth muscle cell differentiationVSMC contractile phenotypeAdipo-R1Smooth muscle cell differentiationAdiponectin levelsSerum hormonesCardioprotective roleHormonal inhibitorCardiovascular diseaseAdiponectinCardioprotective functionControl virusEndothelial cellsVSMC
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
2006
The prostacyclin receptor induces human vascular smooth muscle cell differentiation via PKA
Fetalvero K, Shyu M, Nomikos A, Chiu Y, Wagner R, Powell R, Hwa J, Martin K. The prostacyclin receptor induces human vascular smooth muscle cell differentiation via PKA. The FASEB Journal 2006, 20: a665-a666. DOI: 10.1096/fasebj.20.4.a665-d.Peer-Reviewed Original ResearchVascular smooth muscle cellsHuman vascular smooth muscle cellsCardiovascular eventsHuman vascular smooth muscle cell differentiationProstacyclin receptorVSMC phenotypeSelective COX-2 inhibitorsAdverse cardiovascular eventsSuperficial femoral arteryProstacyclin analogue iloprostCOX-2 inhibitorsSmooth muscle cellsCAMP/PKA signalingVascular smooth muscle cell differentiationSmooth muscle differentiation markersSmooth muscle cell differentiationArterial injuryCardioprotective effectsFemoral arteryAnalogue iloprostClinical trialsH-caldesmonOrgan donorsAnimal modelsNM iloprost
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