2022
BMPR1A promotes ID2–ZEB1 interaction to suppress excessive endothelial to mesenchymal transition
Lee H, Adachi T, Pak B, Park S, Hu X, Choi W, Kowalski PS, Chang CH, Clapham KR, Lee A, Papangeli I, Kim J, Han O, Park J, Anderson DG, Simons M, Jin S, Chun HJ. BMPR1A promotes ID2–ZEB1 interaction to suppress excessive endothelial to mesenchymal transition. Cardiovascular Research 2022, 119: 813-825. PMID: 36166408, PMCID: PMC10409893, DOI: 10.1093/cvr/cvac159.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein Receptors, Type IEndothelial CellsEndotheliumEpithelial-Mesenchymal TransitionHypertension, PulmonaryInhibitor of Differentiation Protein 2LungMicePulmonary Arterial HypertensionReceptor, Transforming Growth Factor-beta Type IIZinc Finger E-box-Binding Homeobox 1ConceptsPathogenesis of PAHPulmonary arterial hypertensionEndothelial cellsOnset of PAHAmeliorate pulmonary arterial hypertensionPotential novel therapeutic targetType 1 receptorType 2 receptorEndothelial-mesenchymal transitionNovel therapeutic targetGrowth factor-beta stimulationSmooth muscle cellsBone morphogenetic proteinPAH patientsArterial hypertensionVascular disordersBMP type 1 receptorsResponse of ECsAdult miceEndoMTTherapeutic targetBeta stimulationPathogenesisMesenchymal transitionMuscle cells
2017
Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin’s glucose-lowering effects
Hwangbo C, Wu J, Papangeli I, Adachi T, Sharma B, Park S, Zhao L, Ju H, Go GW, Cui G, Inayathullah M, Job JK, Rajadas J, Kwei SL, Li MO, Morrison AR, Quertermous T, Mani A, Red-Horse K, Chun HJ. Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin’s glucose-lowering effects. Science Translational Medicine 2017, 9 PMID: 28904225, PMCID: PMC5703224, DOI: 10.1126/scitranslmed.aad4000.Peer-Reviewed Original ResearchConceptsGlucose-lowering effectImpaired glucose utilizationForkhead box protein O1Glucose utilizationType 2 diabetes mellitusEndothelial cellsApelin/APLNRSkeletal muscleTissue fatty acid uptakeType 2 diabetesImportant clinical challengeFatty acid uptakeEndothelial-specific deletionBox protein O1FABP4 inhibitionCardiovascular outcomesPeptide apelinDiabetes mellitusGlucose loweringFatty acidsInsulin sensitivityEndothelial expressionClinical challengeFABP4 expressionMetabolic disorders
2016
MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
Papangeli I, Kim J, Maier I, Park S, Lee A, Kang Y, Tanaka K, Khan OF, Ju H, Kojima Y, Red-Horse K, Anderson DG, Siekmann AF, Chun HJ. MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation. Nature Communications 2016, 7: 11268. PMID: 27068353, PMCID: PMC4832062, DOI: 10.1038/ncomms11268.Peer-Reviewed Original ResearchConceptsRetinal vascular defectsMiR-139-5pG protein-coupled receptorsVascular defectsGPCR crosstalkProtein-coupled receptorsVascular developmentCXCR4 expressionCXCR4 axisCXCR4 signalingDownstream signaling cascadesVascular phenotypePharmacological inhibitionVascular maturationDeficient stateApelinAPLNRLigand-receptor pairsSignaling cascadesInhibitionCXCR4MiceReceptors
2014
Restoration of Impaired Endothelial Myocyte Enhancer Factor 2 Function Rescues Pulmonary Arterial Hypertension
Kim J, Hwangbo C, Hu X, Kang Y, Papangeli I, Mehrotra D, Park H, Ju H, McLean DL, Comhair SA, Erzurum SC, Chun HJ. Restoration of Impaired Endothelial Myocyte Enhancer Factor 2 Function Rescues Pulmonary Arterial Hypertension. Circulation 2014, 131: 190-199. PMID: 25336633, PMCID: PMC4293354, DOI: 10.1161/circulationaha.114.013339.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApelinArteriolesCells, CulturedDisease Models, AnimalDrug Evaluation, PreclinicalEndothelial CellsFibroblast Growth Factor 2HemodynamicsHistone Deacetylase InhibitorsHydroxamic AcidsHypertension, PulmonaryHypertrophy, Right VentricularHypoxiaIntercellular Signaling Peptides and ProteinsMaleMEF2 Transcription FactorsMicroRNAsMonocrotalinePulmonary ArteryPyrrolesRatsRats, Sprague-DawleyRNA InterferenceRNA, Small InterferingTranscription, GeneticConceptsPulmonary arterial hypertensionPulmonary artery endothelial cellsPulmonary vascular homeostasisPAH-pulmonary artery endothelial cellsMyocyte enhancer factor 2Arterial hypertensionCauses of PAHVascular homeostasisExperimental pulmonary hypertension modelsIncreased pulmonary arterial pressurePulmonary artery smooth muscle cellsArtery smooth muscle cellsMEF2 activityRight ventricular failurePulmonary arterial pressurePulmonary hypertension modelPotential therapeutic strategyPotential therapeutic valueSmooth muscle cellsArtery endothelial cellsFactor 2Potential adverse effectsTranscription factor myocyte enhancer factor 2Class IIa HDACsVentricular failure
2013
Apelin-APJ Signaling Is a Critical Regulator of Endothelial MEF2 Activation in Cardiovascular Development
Kang Y, Kim J, Anderson JP, Wu J, Gleim SR, Kundu RK, McLean DL, Kim JD, Park H, Jin SW, Hwa J, Quertermous T, Chun HJ. Apelin-APJ Signaling Is a Critical Regulator of Endothelial MEF2 Activation in Cardiovascular Development. Circulation Research 2013, 113: 22-31. PMID: 23603510, PMCID: PMC3739451, DOI: 10.1161/circresaha.113.301324.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAdipokinesAnimalsApelinApelin ReceptorsCardiovascular AbnormalitiesCardiovascular SystemEndocardiumEndothelium, VascularFemaleFetal HeartGene Expression Regulation, DevelopmentalGenes, LethalGTP-Binding Protein alpha Subunits, G12-G13Histone DeacetylasesIntercellular Signaling Peptides and ProteinsKruppel-Like Transcription FactorsMaleMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, KnockoutMyogenic Regulatory FactorsPhosphorylationProtein Processing, Post-TranslationalReceptors, G-Protein-CoupledSignal TransductionTranscription, GeneticConceptsCardiovascular developmentVentricular wall developmentMyocyte enhancer factor 2Embryonic lethal phenotypeCardiovascular developmental defectsFactor 2Apelin-APJHistone deacetylase 4MEF2 functionModel organismsLethal phenotypeEmbryonic lethalityTranscriptional targetsMEF2 activationKrüppel-like factor 2Wall developmentHDAC5 phosphorylationCushion formationNuclear localizationVascular smooth muscle cellsEndothelial cellsDevelopmental defectsMolecular mechanismsCritical regulatorLigand apelin
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