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
2023
Role of ascorbic acid in cardiac allograft vasculopathy
Chang A, Martin K, Colvin M, Bellumkonda L. Role of ascorbic acid in cardiac allograft vasculopathy. Clinical Transplantation 2023, 37: e15153. PMID: 37792313, DOI: 10.1111/ctr.15153.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathySmooth muscle cell apoptosisAllograft vasculopathyDisease processMuscle cell apoptosisSignificant long-term morbidityCell apoptosisProgressive fibroproliferative diseasePost-transplant carePost-transplant managementLong-term morbiditySmall clinical trialsChallenging disease processVascular smooth muscle cell apoptosisHeart transplantationCAV progressionEndothelial dysfunctionRapamycin inhibitorsClinical trialsIntimal thickeningPrevents developmentInterferon γRodent modelsIntimal hyperplasiaMTOR inhibitorsSerum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability
Zhang J, Wu Q, Hu X, Wang Y, Lu J, Chakraborty R, Martin K, Guo S. Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability. Stem Cells 2023, 41: 907-915. PMID: 37386941, PMCID: PMC11009695, DOI: 10.1093/stmcls/sxad051.Peer-Reviewed Original ResearchConceptsMouse pluripotent stem cellsSerum response factorPluripotent stem cellsCell fate stabilityRole of SRFGene expression noiseHeterogeneous gene expressionResponse factorStem cellsNaïve pluripotencyCell state heterogeneityLineage primingExpression noiseActin dynamicsCellular statesPluripotent cellsSRF functionCell statesMechanical signalingGene expressionFunctional modulationCentral mediatorSerum-containing culturesState heterogeneityCellsSex hormones impact early maturation and immune response in the arteriovenous fistula mouse model
Satam K, Ohashi Y, Thaxton C, Gonzalez L, Setia O, Bai H, Aoyagi Y, Xie Y, Zhang W, Yatsula B, Martin K, Cai Y, Dardik A. Sex hormones impact early maturation and immune response in the arteriovenous fistula mouse model. AJP Heart And Circulatory Physiology 2023, 325: h77-h88. PMID: 37145957, PMCID: PMC10243550, DOI: 10.1152/ajpheart.00049.2023.Peer-Reviewed Original ResearchConceptsIntact female miceAVF maturationSex hormonesT cellsFemale miceArteriovenous fistulaMale miceMouse modelHigher IL-10Arteriovenous fistula creationImmune cell recruitmentSex-specific therapiesHormone receptor signalingSex differencesHuman AVF maturationAVF surgeryMale patientsClinical outcomesFemale patientsFistula maturationIL-10C57BL/6 miceInferior outcomesVenous adaptationFistula creationThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis“Cre”ating New Tools for Smooth Muscle Analysis
O’Brien B, Martin K, Offermanns S. “Cre”ating New Tools for Smooth Muscle Analysis. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: 212-214. PMID: 36601960, PMCID: PMC10112502, DOI: 10.1161/atvbaha.122.318855.Peer-Reviewed Original Research
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
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 miceHyperplasiaTechnical Feasibility of a Murine Model of Sleeve Gastrectomy with Ileal Transposition
Ying LD, Breuer GA, Hubbard MO, Nadzam GS, Hwa J, Martin KA. Technical Feasibility of a Murine Model of Sleeve Gastrectomy with Ileal Transposition. Obesity Surgery 2018, 29: 593-600. PMID: 30353248, PMCID: PMC6365182, DOI: 10.1007/s11695-018-3555-7.Peer-Reviewed Original ResearchConceptsIleal transpositionSleeve gastrectomySham surgeryMouse modelReproducible mouse modelIntestinal identityQuantitative polymerase chain reactionBackgroundSleeve gastrectomySham procedureC57BL/6J miceObesogenic dietPolymerase chain reactionGastrectomyMurine modelPorcine modelWeight gainWeight lossMiceChain reactionMolecular pathwaysGene expression analysisWeeksFuture studiesLong-term survivabilityTechnical feasibility
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 thrombosisClonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, Wu CL, Sano S, Muralidharan S, Rius C, Vuong J, Jacob S, Muralidhar V, Robertson AA, Cooper MA, Andrés V, Hirschi KK, Martin KA, Walsh K. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 2017, 355: 842-847. PMID: 28104796, PMCID: PMC5542057, DOI: 10.1126/science.aag1381.Peer-Reviewed Original ResearchConceptsTET2-deficient cellsLow-density lipoprotein receptor-deficient miceLipoprotein receptor-deficient miceClonal hematopoiesisBlood cellsAtherosclerotic cardiovascular diseaseAtherosclerotic plaque sizeReceptor-deficient miceBone marrow reconstitutionInterleukin-1β secretionMutant blood cellsAtherosclerosis developmentNLRP3 inhibitorAtheroprotective activityCardiovascular diseaseMarrow reconstitutionChimeric micePlaque sizeClonal expansionMiceMarked increaseCausal roleTET2 deficiencySomatic mutationsHematopoietic cells
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
2014
Epigenetic regulation of smooth muscle cell plasticity
Liu R, Leslie KL, Martin KA. Epigenetic regulation of smooth muscle cell plasticity. Biochimica Et Biophysica Acta 2014, 1849: 448-453. PMID: 24937434, PMCID: PMC4552189, DOI: 10.1016/j.bbagrm.2014.06.004.Peer-Reviewed Original ResearchConceptsSMC plasticityEpigenetic regulationSmooth muscle cellsCell plasticitySmooth Muscle Cell PlasticityRegulatory cis elementsCell typesDNA demethylation pathwayLevel of epigeneticsMuscle cell plasticityMature cell typesKey transcription factorMajor cell typesHistone modificationsNovel target moleculesDNA methylationTranscription factorsEnvironmental stressCis elementsPhenotypic statesDemethylation pathwaySMC phenotypeMolecular mechanismsAdult bodyRemarkable plasticity
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
2011
Prostacyclin receptor regulation--from transcription to trafficking.
Midgett C, Stitham J, Martin K, Hwa J. Prostacyclin receptor regulation--from transcription to trafficking. 2011, 11: 517-28. PMID: 21707517, PMCID: PMC3647249, DOI: 10.2174/156652411800615144.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMouse knockout studiesReceptor regulationTransmembrane G-proteinKnockout studiesG proteinsCell surfaceRegulatory processesNon-selective COX-1/COXCorrect functionTranscriptionHigh cardiovascular risk patientsImportant receptorProstacyclin receptorImportant cardioprotective rolePrevention of atherothrombosisCardiovascular risk patientsIncreased cardiovascular eventsCOX-1/COXRegulationReceptorsCardiovascular eventsRisk patientsReceptor dysfunctionCardioprotective roleIP receptor
2010
Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors
Fei D, Li H, Kozul C, Black K, Singh S, Gosse J, DiRenzo J, Martin K, Wang B, Hamilton J, Karagas M, Robbins D. Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors. Cancer Research 2010, 70: 1981-1988. PMID: 20179202, PMCID: PMC2831120, DOI: 10.1158/0008-5472.can-09-2898.Peer-Reviewed Original ResearchConceptsArsenic exposureBladder cancerEnvironmental toxicant arsenicBladder cancer patientsSignificant health problemVariety of tumorsHedgehog signalingCancer patientsHealth problemsHigh levelsTumor samplesCancerHedgehog activitySame cancerHuman carcinogenesisMillions of peopleEtiologyTumorsExposureProgressionHedgehogTissue culture cellsActivationSignalingPatients
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