2015
Programming and reprogramming a human heart cell
Sahara M, Santoro F, Chien K. Programming and reprogramming a human heart cell. The EMBO Journal 2015, 34: 710-738. PMID: 25712211, PMCID: PMC4369310, DOI: 10.15252/embj.201490563.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStem cell biologyCardiac regenerative therapeuticsHuman heart cellsCardiac regenerative medicineHuman cardiogenesisMolecular programsCell biologyRegenerative therapeuticsCardiac regenerationHeart cellsRegenerative medicineDevelopmental cardiologyLatest discoveriesNovel therapeutic toolDiseased heartCardiac muscleCellsCardiogenesisTherapeutic strategiesClinical practiceTherapeutic toolBiologyModest outcomesCurrent controversiesDeeper understanding
2014
Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells
Sahara M, Hansson E, Wernet O, Lui K, Später D, Chien K. Manipulation of a VEGF-Notch signaling circuit drives formation of functional vascular endothelial progenitors from human pluripotent stem cells. Cell Research 2014, 24: 820-841. PMID: 24810299, PMCID: PMC4085760, DOI: 10.1038/cr.2014.59.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBone Morphogenetic Protein 4CadherinsCell DifferentiationCell LineEmbryonic Stem CellsEndothelial CellsEndothelium, VascularGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMicePluripotent Stem CellsReceptors, NotchSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsHuman pluripotent stem cellsPluripotent stem cellsEndothelial lineage cellsEndothelial progenitorsLineage cellsStem cellsVascular endothelial progenitorsVE-cadherin promoterEndothelial cellsGreen fluorescent protein expressionFluorescent protein expressionBioactive small moleculesFunctional vessel networksMesodermal precursorsReporter cell lineDrive formationEndothelial lineageGSK-3β inhibitorDifferentiation protocolsMature endothelial cellsAttractive cell populationRapid large-scale productionEfficient differentiationEndothelial differentiationPharmaceutical inhibition
2013
Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation
Sahara M, Ikutomi M, Morita T, Minami Y, Nakajima T, Hirata Y, Nagai R, Sata M. Deletion of angiotensin-converting enzyme 2 promotes the development of atherosclerosis and arterial neointima formation. Cardiovascular Research 2013, 101: 236-246. PMID: 24193738, DOI: 10.1093/cvr/cvt245.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin-Converting Enzyme 2AnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCell ProliferationCells, CulturedDisease Models, AnimalFemoral ArteryGene DeletionGenetic Predisposition to DiseaseInflammation MediatorsJNK Mitogen-Activated Protein KinasesMacrophagesMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaPeptidyl-Dipeptidase APhenotypePlaque, AtheroscleroticProtein Kinase InhibitorsRNA InterferenceSignal TransductionTransfectionVascular System InjuriesConceptsVascular smooth muscle cellsAortic vascular smooth muscle cellsArterial neointima formationVascular diseaseACE2 deficiencyVascular lesionsEnzyme 2Neointima formationApolipoprotein E knockout miceVascular cell adhesion moleculeACE2 KO miceLarge vascular lesionsAngiotensin II levelsRenin-angiotensin systemE knockout miceAortic atherosclerotic plaquesPro-inflammatory phenotypeRole of ACE2Development of atherosclerosisInflammation-related genesArterial neointimal hyperplasiaTumor necrosis factorSmooth muscle cellsPrimary bone marrow macrophagesDeletion of angiotensin
2012
Nicorandil Attenuates Monocrotaline-Induced Vascular Endothelial Damage and Pulmonary Arterial Hypertension
Sahara M, Sata M, Morita T, Hirata Y, Nagai R. Nicorandil Attenuates Monocrotaline-Induced Vascular Endothelial Damage and Pulmonary Arterial Hypertension. PLOS ONE 2012, 7: e33367. PMID: 22479390, PMCID: PMC3316574, DOI: 10.1371/journal.pone.0033367.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntihypertensive AgentsApoptosisBlotting, WesternCaspase 3Cells, CulturedDrug Therapy, CombinationEndothelium, VascularEnzyme InhibitorsFamilial Primary Pulmonary HypertensionGlyburideHuman Umbilical Vein Endothelial CellsHumansHypertension, PulmonaryInjections, IntraperitonealMaleMAP Kinase Signaling SystemMonocrotalineNG-Nitroarginine Methyl EsterNicorandilPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRandom AllocationRatsRats, Sprague-DawleySignal TransductionVentricular PressureConceptsRight ventricular systolic pressurePulmonary arterial hypertensionHuman umbilical vein endothelial cellsVascular endothelial damageMCT injectionArterial hypertensionEndothelial damageNitro-L-arginine methyl esterNitric oxide synthase inhibitorBeneficial effectsEndothelial NOS expressionVentricular systolic pressureVehicle-treated groupChannel blocker glibenclamideOxide synthase inhibitorChannel opener nicorandilSprague-Dawley ratsCaspase-3 expressionAnti-apoptotic effectsUmbilical vein endothelial cellsPromising therapeutic potentialBcl-2 expressionAnti-apoptotic factorsNicorandil administrationVein endothelial cells
2010
A Phosphodiesterase-5 Inhibitor Vardenafil Enhances Angiogenesis Through a Protein Kinase G-Dependent Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Pathway
Sahara M, Sata M, Morita T, Nakajima T, Hirata Y, Nagai R. A Phosphodiesterase-5 Inhibitor Vardenafil Enhances Angiogenesis Through a Protein Kinase G-Dependent Hypoxia-Inducible Factor-1/Vascular Endothelial Growth Factor Pathway. Arteriosclerosis Thrombosis And Vascular Biology 2010, 30: 1315-1324. PMID: 20413734, DOI: 10.1161/atvbaha.109.201327.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsCapillariesCell HypoxiaCell MovementCells, CulturedCollateral CirculationCyclic GMPCyclic GMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 5Disease Models, AnimalEndothelial CellsGreen Fluorescent ProteinsHindlimbHumansHypoxia-Inducible Factor 1, alpha SubunitImidazolesIschemiaMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMice, TransgenicMuscle, SkeletalNeovascularization, PhysiologicNitric Oxide Synthase Type IIIPhosphodiesterase 5 InhibitorsPhosphodiesterase InhibitorsPiperazinesRecovery of FunctionRegional Blood FlowRNA InterferenceSignal TransductionStem CellsSulfonesTime FactorsTransfectionTriazinesVardenafil DihydrochlorideVascular Endothelial Growth Factor AConceptsEndothelial progenitor cellsVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayIschemia-induced angiogenesisGrowth factor pathwaysIschemic muscleMobilization of EPCsSca-1/flkFactor pathwaySoluble guanylate cyclase inhibitorEndothelial nitric oxide synthasePhosphodiesterase-5 inhibitor vardenafilRight femoral arteryBlood flow recoveryEffect of vardenafilPhosphodiesterase-5 inhibitionUnilateral hindlimb ischemiaGuanylate cyclase inhibitorVascular endothelial growth factorNitric oxide synthaseUpregulated protein expressionProtein kinase G inhibitorIschemic cardiovascular diseaseCapillary-like tube formationEndothelial growth factor