2024
Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis
Dave J, Chakraborty R, Agyemang A, Ntokou A, Saito J, Ballabh P, Martin K, Greif D. Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis. Stroke 2024, 55: 2340-2352. PMID: 39129597, PMCID: PMC11347087, DOI: 10.1161/strokeaha.123.045248.Peer-Reviewed Original ResearchAngiopoietin-2Germinal matrix hemorrhage-intraventricular hemorrhagePerinatal lethalityEndothelial cell hyperproliferationEndothelial cellsBrain pericytesGenetic inhibitionVascular cellsBlood-brain barrier integrityBlood-brain barrier developmentBrain vascular cellsAbnormal vessel morphologyVessel morphologyProlonged survivalRegulating cross-talkMutant endothelial cellsHuman brain pericytesGerminal matrixCell hyperproliferationPhosphorylates Tie2Embryonic miceCellular sourceBarrier integrityGenetic ablationTherapeutic effectA 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 ResearchAbstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity
Chatterjee P, Chakraborty R, Sizer A, Xie Y, Hwa J, Martin K. Abstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a2121-a2121. DOI: 10.1161/atvb.44.suppl_1.2121.Peer-Reviewed Original ResearchRNA-seqPhenotypic plasticityEpigenetic regulationH3K9me3 repressive marksRNA-seq transcriptomicsContractile genesEpigenetic transcriptional repressionCell phenotypic plasticityH3K9me3 markExpression of SUV39H1Repressive marksTranscriptional repressionChromatin immunoprecipitationHistone methyltransferaseDedifferentiation in vitroIn vivoSUV39H1 knockdownH3K9me3MRNA stabilitySUV39H1Gene expressionPlasticity of vascular smooth muscle cellsRegulation of Klf4GenesH3K9me3 expressionAbstract 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
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 inhibitorsTNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
Boutagy N, Fowler J, Grabinska K, Cardone R, Sun Q, Vazquez K, Whalen M, Zhu X, Chakraborty R, Martin K, Simons M, Romanoski C, Kibbey R, Sessa W. TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2218150120. PMID: 37695914, PMCID: PMC10515159, DOI: 10.1073/pnas.2218150120.Peer-Reviewed Original ResearchConceptsPyruvate dehydrogenase kinase 4Dehydrogenase kinase 4Lon proteasePyruvate dehydrogenase activityHistone acetylationMitochondrial metabolismKinase 4Specific gene lociPDH fluxEndothelial cellsSiRNA-mediated knockdownAcetyl-CoA generationLysine 27Gene transcriptionTCA fluxRNA sequencingHuman umbilical vein endothelial cellsProtein degradationHistone 3Gene locusUmbilical vein endothelial cellsNF-κB-dependent mechanismTricarboxylic acid cycle fluxVein endothelial cellsActive subunitSerum 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
2022
Better together
Martin K, Hwa J. Better together. Science 2022, 378: 442-442. PMID: 36302027, DOI: 10.1126/science.adf4466.Peer-Reviewed Original ResearchA guide to molecular and functional investigations of platelets to bridge basic and clinical sciences
Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nature Cardiovascular Research 2022, 1: 223-237. PMID: 37502132, PMCID: PMC10373053, DOI: 10.1038/s44161-022-00021-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVascular smooth muscle cellsPlatelet functional assaysCoronavirus disease 2019Smooth muscle cellsImmune cellsImmune regulationVascular remodelingDisease 2019Pathophysiological processesTranslational relevancePatient diagnosisFlow cytometryMuscle cellsPlatelet biologyFunctional assaysPlatelet investigationsHomeostatic processesPlateletsPhenotypic heterogeneityFunctional stateClinical scienceCellsAdditional roleThrombosisSuch diverse functions
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 failureTargeting smooth muscle cell phenotypic switching in vascular disease
JVS-Vascular Science 2021;2:79-94.Books
2020
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, Krause DS, Lee AI, Halene S, Martin KA, Chun HJ, Hwa J. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nature Reviews Cardiology 2020, 18: 194-209. PMID: 33214651, PMCID: PMC7675396, DOI: 10.1038/s41569-020-00469-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdministration, InhalationAnticoagulantsBlood Coagulation DisordersBlood Platelet DisordersCOVID-19COVID-19 Drug TreatmentEndothelium-Dependent Relaxing FactorsEndothelium, VascularEpoprostenolHeart Disease Risk FactorsHumansIloprostInflammationNitric OxidePlatelet Aggregation InhibitorsSARS-CoV-2Systemic Inflammatory Response SyndromeThrombosisThrombotic MicroangiopathiesVascular DiseasesVasodilator AgentsVenous ThromboembolismConceptsCardiovascular risk factorsRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2Pre-existing cardiovascular diseaseAcute respiratory syndrome coronavirus 2Traditional cardiovascular risk factorsAcute respiratory distress syndromeRespiratory syndrome coronavirus 2Respiratory distress syndromeManagement of patientsSyndrome coronavirus 2COVID-19 pathologyCoronavirus disease 2019Potential therapeutic strategyCytokine stormEndothelial dysfunctionThrombotic complicationsDistress syndromeExcessive inflammationCoronavirus 2Severe outcomesAdvanced ageCardiovascular diseaseDisease 2019Circular 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 dataTCF21
Xie Y, Martin KA. TCF21. Circulation Research 2020, 126: 530-532. PMID: 32078454, PMCID: PMC7041869, DOI: 10.1161/circresaha.120.316533.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