2023
The 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 ResearchMeSH KeywordsAgedAnimalsAtherosclerosisBone MarrowHumansIntegrin beta3MiceMuscle, SmoothMyocytes, Smooth MusclePlaque, AtheroscleroticConceptsAtherosclerotic 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
2022
Vascular pathobiology of pulmonary hypertension
Gallardo-Vara E, Ntokou A, Dave J, Jovin D, Saddouk F, Greif D. Vascular pathobiology of pulmonary hypertension. The Journal Of Heart And Lung Transplantation 2022, 42: 544-552. PMID: 36604291, PMCID: PMC10121751, DOI: 10.1016/j.healun.2022.12.012.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionCell typesSmooth muscle cell proliferationEndothelial cell dysfunctionMuscle cell proliferationKruppel-like factor 4Extracellular matrix remodelingHypoxia-inducible factorBox proteinBlood pressurePulmonary arteryInflammatory cellsPulmonary vasculatureMain cell typesVascular pathogenesisVasoactive moleculesCell dysfunctionClinical impactVascular pathobiologyPathological remodelingIntercellular crosstalkLethal diseaseMesenchymal transitionMatrix remodelingGrowth factorHistone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity
Chakraborty R, Ostriker AC, Xie Y, Dave JM, Gamez-Mendez A, Chatterjee P, Abu Y, Valentine J, Lezon-Geyda K, Greif DM, Schulz VP, Gallagher PG, Sessa WC, Hwa J, Martin KA. Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity. Circulation 2022, 145: 1720-1737. PMID: 35502657, DOI: 10.1161/circulationaha.121.057599.Peer-Reviewed Original ResearchConceptsHistone acetylationContractile genesContractile protein expressionPhenotypic switchingHistone acetyl transferase p300Human intimal hyperplasiaPlatelet-derived growth factor treatmentAcetyl transferase p300Key regulatory mechanismSmooth muscle cell phenotypeP300 expressionP300-dependent acetylationSmooth muscle plasticityDistinct functional interactionsMuscle cell phenotypeProtein expressionIntimal hyperplasiaRole of p300Methylcytosine dioxygenase TET2Chromatin modificationsEpigenetic regulationVSMC phenotypic switchingSpecific histoneCardiovascular diseaseMaster regulator
2021
SNCs meet SMCs in the atherosclerotic plaque
Kabir I, Greif D. SNCs meet SMCs in the atherosclerotic plaque. Nature Aging 2021, 1: 631-633. PMID: 36540165, PMCID: PMC9762735, DOI: 10.1038/s43587-021-00096-6.Commentaries, Editorials and LettersAtherosclerosisCells, CulturedCellular SenescenceHumansMyocytes, Smooth MusclePlaque, Atherosclerotic
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 wall
2018
Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells
Misra A, Feng Z, Chandran RR, Kabir I, Rotllan N, Aryal B, Sheikh AQ, Ding L, Qin L, Fernández-Hernando C, Tellides G, Greif DM. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nature Communications 2018, 9: 2073. PMID: 29802249, PMCID: PMC5970166, DOI: 10.1038/s41467-018-04447-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisBone Marrow TransplantationCell MovementCell ProliferationCell TransdifferentiationCells, CulturedCholesterolDisease Models, AnimalFemaleHumansIntegrin beta3MacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticConceptsSmooth muscle cellsPre-existing smooth muscle cellsAtherosclerotic plaquesPlaque cellsToll-like receptor 4 expressionSmooth muscle-derived cellsBone marrow-derived cellsSingle smooth muscle cellsAtherosclerotic plaque cellsReceptor 4 expressionMarrow-derived cellsBone marrow resultsMuscle-derived cellsIntegrin β3 levelsMacrophage-like phenotypeCD36 levelsMarrow resultsSMC proliferationPlaque coresSMC progenitorsMuscle cellsIntegrin β3AtherogenesisPlaquesIntegrin beta3Cell Autonomous and Non-cell Autonomous Regulation of SMC Progenitors in Pulmonary Hypertension
Sheikh AQ, Saddouk FZ, Ntokou A, Mazurek R, Greif DM. Cell Autonomous and Non-cell Autonomous Regulation of SMC Progenitors in Pulmonary Hypertension. Cell Reports 2018, 23: 1152-1165. PMID: 29694892, PMCID: PMC5959296, DOI: 10.1016/j.celrep.2018.03.043.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionMyeloid cellsPlatelet-derived growth factor receptor βGrowth factor receptor βKruppel-like factor 4Muscle cell markersAttractive therapeutic targetHypoxia-inducible factor-1Vascular muscularizationDistal migrationNormal lungSmall arteriolesMuscle expansionHypertensionTherapeutic targetNon-cell autonomous pathwaysReceptor βCell expressionCell inductionCell markersSMC progenitorsEndothelial cellsFactor 1Factor 4Muscularization
2016
Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra A, Sheikh AQ, Kumar A, Luo J, Zhang J, Hinton RB, Smoot L, Kaplan P, Urban Z, Qyang Y, Tellides G, Greif DM. Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. Journal Of Experimental Medicine 2016, 213: 451-463. PMID: 26858344, PMCID: PMC4813675, DOI: 10.1084/jem.20150688.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMutant miceTherapeutic strategiesAortic stenosis patientsAortic smooth muscle cellsSupravalvular aortic stenosisAttractive therapeutic strategyIntegrin β3 levelsAortic pathologyAortic stenosisStenosis patientsArterial diseaseLumen lossPathological featuresArterial mediaLarge arteriesAortic mediaElastin deficiencyPharmacological inhibitionMuscle cellsStenosisMicePathological stenosisExplant culturesSVAS patients
2015
Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension
Sheikh AQ, Misra A, Rosas IO, Adams RH, Greif DM. Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension. Science Translational Medicine 2015, 7: 308ra159. PMID: 26446956, PMCID: PMC4629985, DOI: 10.1126/scitranslmed.aaa9712.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsKruppel-like factor 4Pulmonary hypertensionSmooth muscleHypoxia-induced pulmonary hypertensionPathogenesis of PHPulmonary artery blood pressureSMC progenitorsArteriole smooth muscleArtery blood pressureSmooth muscle cell progenitorsCardiovascular disease pathogenesisPlatelet-derived growth factor receptorHypoxia-induced expressionGrowth factor receptorPH patientsBlood pressurePulmonary arteriolesVascular disordersTherapeutic strategiesDisease pathogenesisKLF4 levelsKLF4 expressionDistal extensionMuscle cells
2014
Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension
Sheikh AQ, Lighthouse JK, Greif DM. Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension. Cell Reports 2014, 6: 809-817. PMID: 24582963, PMCID: PMC4015349, DOI: 10.1016/j.celrep.2014.01.042.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCell Growth ProcessesCell HypoxiaHumansHypertension, PulmonaryMiceMyocytes, Smooth MuscleMyofibroblastsConceptsPulmonary artery hypertensionArtery hypertensionArteriole smooth muscle cellsSmooth muscle accumulationPulmonary artery complianceModest clinical benefitStrong independent predictorMuscle cell dedifferentiationSmooth muscle cellsPulmonary hypertensionArtery complianceIndependent predictorsClinical benefitPulmonary vasculatureDistal migrationVascular disordersAlveolar myofibroblastsSmooth muscleHypertensionMuscle accumulationMuscularizationMuscle cellsCell dedifferentiationPoor understandingAtherosclerosis
2013
Development and pathologies of the arterial wall
Seidelmann SB, Lighthouse JK, Greif DM. Development and pathologies of the arterial wall. Cellular And Molecular Life Sciences 2013, 71: 1977-1999. PMID: 24071897, PMCID: PMC11113178, DOI: 10.1007/s00018-013-1478-y.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenic ProteinsAnimalsArteriesCardiovascular DiseasesCell DifferentiationCell LineageEndothelial CellsEndothelium, VascularGene Expression Regulation, DevelopmentalHumansMorphogenesisMuscle, Smooth, VascularMyocytes, Smooth MuscleNeovascularization, PathologicNeovascularization, PhysiologicConceptsAdventitial progenitor cellsDevastating vascular diseaseDevelopmental biologyWall developmentSmooth muscle cell originHuman diseasesExtracellular matrixMuscle cell originProcess of angiogenesisProgenitor cellsEndothelial networksDisease mechanismsNovel therapeutic strategiesDevelopmental studiesEndothelial cellsSmooth muscleCellsMorphogenesisTherapeutic strategiesCell originBiologyDifferentiationVascular diseaseVascular wallVascular wall abnormalities
2012
An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension
Kim J, Kang Y, Kojima Y, Lighthouse JK, Hu X, Aldred MA, McLean DL, Park H, Comhair SA, Greif DM, Erzurum SC, Chun HJ. An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension. Nature Medicine 2012, 19: 74-82. PMID: 23263626, PMCID: PMC3540168, DOI: 10.1038/nm.3040.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApelinCell MovementCell ProliferationCells, CulturedCulture Media, ConditionedDown-RegulationEndothelial CellsFamilial Primary Pulmonary HypertensionFibroblast Growth Factor 2HumansHypertension, PulmonaryIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMuscle, Smooth, VascularMyocytes, Smooth MusclePulmonary ArteryRatsReceptor, Fibroblast Growth Factor, Type 1RNA InterferenceRNA, Small InterferingSignal TransductionVascular DiseasesConceptsPulmonary arterial hypertensionArterial hypertensionVascular smooth muscle cellsPulmonary endothelial cellsSmooth muscle cellsEndothelial cell proliferationPulmonary hypertensionPeptide apelinCytokine productionRat modelVascular homeostasisHypertensionMiR-503MiR-424Endothelial cellsCell proliferation