2021
A neutrophil activation signature predicts critical illness and mortality in COVID-19
Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, Simonov M, Chang CH, Zhang H, Shallow M, Bahel P, Owusu K, Yamamoto Y, Arora T, Atri DS, Patel A, Gbyli R, Kwan J, Won CH, Dela Cruz C, Price C, Koff J, King BA, Rinder HM, Wilson FP, Hwa J, Halene S, Damsky W, van Dijk D, Lee AI, Chun HJ. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances 2021, 5: 1164-1177. PMID: 33635335, PMCID: PMC7908851, DOI: 10.1182/bloodadvances.2020003568.Peer-Reviewed Original ResearchConceptsCritical illnessHealth system databaseNeutrophil activationCOVID-19Neutrophil activation signatureSevere COVID-19Intensive care unitGranulocyte colony-stimulating factorHigh mortality rateColony-stimulating factorSystem databaseHepatocyte growth factorClinical decompensationNeutrophil countImmune hyperactivationCare unitEarly elevationLipocalin-2Interleukin-8Longitudinal cohortClinical dataMortality ratePatientsIllnessActivation signature
2020
Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study
Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, Baluha A, Bar N, Bona RD, Burns AJ, Dela Cruz CS, Dumont A, Halene S, Hwa J, Koff J, Menninger H, Neparidze N, Price C, Siner JM, Tormey C, Rinder HM, Chun HJ, Lee AI. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. The Lancet Haematology 2020, 7: e575-e582. PMID: 32619411, PMCID: PMC7326446, DOI: 10.1016/s2352-3026(20)30216-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBetacoronavirusBiomarkersBlood Coagulation DisordersCoronavirus InfectionsCOVID-19Critical IllnessCross-Sectional StudiesEndothelium, VascularFemaleFollow-Up StudiesHumansIntensive Care UnitsMaleMiddle AgedPandemicsPneumonia, ViralPrognosisSARS-CoV-2Vascular DiseasesYoung AdultConceptsCOVID-19-associated coagulopathyNon-ICU patientsIntensive care unitKaplan-Meier analysisSoluble P-selectinCross-sectional studyPlatelet activationHospital dischargeICU patientsSoluble thrombomodulinEndothelial cellsVWF antigenCOVID-19P-selectinSingle-center cross-sectional studyLaboratory-confirmed COVID-19Medical intensive care unitSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesisVon Willebrand factor antigenSoluble thrombomodulin concentrationsVWF antigen concentrationEndothelial cell injurySoluble CD40 ligandMicrovascular complicationsAdult patients
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
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