2024
Endothelial HIFα-PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension
Saddouk F, Kuzemczak A, Saito J, Greif D. Endothelial HIFα-PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension. JCI Insight 2024, 9: e162449. PMID: 38652543, PMCID: PMC11141934, DOI: 10.1172/jci.insight.162449.Peer-Reviewed Original ResearchSmooth muscle cellsArteriole smooth muscle cellsPulmonary hypertensionPlatelet-derived growth factor-BDistal muscularizationSugen 5416Endothelial cellsHuman idiopathic pulmonary arterial hypertensionHypoxia-induced pulmonary vascular remodelingPulmonary artery smooth muscle cellsIdiopathic pulmonary arterial hypertensionHypoxia-inducible factor (HIF)-1aArtery smooth muscle cellsDistal pulmonary arteriolesPulmonary arterial hypertensionPulmonary vascular remodelingDeletion of Hif1aLung endothelial cellsGrowth factor BEC-specific deletionPulmonary arteriolesArterial hypertensionLung lysatesMuscle cellsVascular remodeling
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 factor
2021
Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension
Ntokou A, Dave JM, Kauffman AC, Sauler M, Ryu C, Hwa J, Herzog EL, Singh I, Saltzman WM, Greif DM. Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension. JCI Insight 2021, 6: e139067. PMID: 33591958, PMCID: PMC8026182, DOI: 10.1172/jci.insight.139067.Peer-Reviewed Original ResearchConceptsRight ventricle hypertrophyPulmonary hypertensionDistal muscularizationSmooth muscle cellsHypoxia-inducible factor 2APulmonary arterial hypertension patientsLysM-Cre miceArterial hypertension patientsHuman pulmonary hypertensionHypoxia-inducible factor 1aPlatelet-derived growth factorMacrophage-conditioned mediumVentricle hypertrophyHypertension patientsDistal arteriolesMacrophage accumulationFl miceCardiovascular diseaseInterventional strategiesMuscularizationHypoxia exposureExcess macrophagesSMC proliferationLethal diseaseMuscle cells
2020
Specialized Smooth Muscle Cell Progenitors in Pulmonary Hypertension
Saddouk F, Ntokou A, Greif D. Specialized Smooth Muscle Cell Progenitors in Pulmonary Hypertension. 2020, 25-30. DOI: 10.1007/978-981-15-1185-1_4.ChaptersSmooth muscle cellsPulmonary hypertensionNormal lungArteriole smooth muscle cellsPulmonary artery complianceSmooth muscle cell progenitorsStrong independent predictorPlatelet-derived growth factor receptorKruppel-like factor 4Diverse cardiovascular diseasesHypoxia-inducible factorGrowth factor receptorArtery complianceIndependent predictorsTherapeutic optionsIdiopathic formCardiovascular diseaseDependent signaling contributesSignaling contributesHypertensionSMC progenitorsMuscle cellsFactor receptorNon-cell autonomous mannerCell progenitors
2018
Cell 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
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 ResearchConceptsPulmonary 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
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