Featured Publications
The evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammationLiver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjuryAlcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis
Su T, Yang Y, Lai S, Jeong J, Jung Y, McConnell M, Utsumi T, Iwakiri Y. Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 1139-1161. PMID: 33340713, PMCID: PMC7903131, DOI: 10.1016/j.jcmgh.2020.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillariesCarbon TetrachlorideEndothelial CellsGene Expression RegulationLiver CirrhosisMiceSingle-Cell AnalysisTranscriptomeConceptsLiver sinusoidal endothelial cellsCirrhotic miceSinusoidal endothelial cellsLiver cirrhosisEndothelial cellsIntrahepatic vascular resistanceCarbon tetrachloride inhalationNovel therapeutic strategiesNitric oxide productionCirrhotic mouse liverEC populationsVascular resistanceClinical complicationsLiver fibrosisTherapeutic strategiesCirrhosisOxide productionEndocytic receptorMiceAbstractTextZone 3Extracellular matrix genesVascular ECsLymphatic ECsMouse liver
2023
Endotheliopathy of liver sinusoidal endothelial cells in liver disease
Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathology International 2023, 73: 381-393. PMID: 37589433, DOI: 10.1111/pin.13361.Peer-Reviewed Original ResearchConceptsLiver diseaseSinusoidal endothelial cellsEndothelial cellsLiver injuryLiver tissueIntercellular adhesion molecule-1Improvement of thrombocytopeniaNeutrophil chemotactic mediatorsChronic hepatitis CLiver sinusoidal endothelial cellsSetting of inflammationSevere hepatic inflammationAdhesion molecule-1Largest solid organPotential therapeutic strategyVascular endothelial cellsVon Willebrand factorHepatitis CNeutrophil accumulationHepatic inflammationChemotactic mediatorsIL-6Antithrombotic factorsChemokine ligandSolid organs
2019
Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver
Cui J, Piotrowski-Daspit AS, Zhang J, Shao M, Bracaglia LG, Utsumi T, Seo YE, DiRito J, Song E, Wu C, Inada A, Tietjen GT, Pober JS, Iwakiri Y, Saltzman WM. Poly(amine-co-ester) nanoparticles for effective Nogo-B knockdown in the liver. Journal Of Controlled Release 2019, 304: 259-267. PMID: 31054286, PMCID: PMC6613984, DOI: 10.1016/j.jconrel.2019.04.044.Peer-Reviewed Original Research
2018
Lymphatics in the liver
Tanaka M, Iwakiri Y. Lymphatics in the liver. Current Opinion In Immunology 2018, 53: 137-142. PMID: 29772409, PMCID: PMC6986420, DOI: 10.1016/j.coi.2018.04.028.BooksMeSH KeywordsAnimalsCarcinoma, HepatocellularEndothelial CellsHepatitis, Viral, HumanHumansLiverLiver CirrhosisLymphangiogenesisLymphatic VesselsConceptsHepatic lymphatic systemLymphatic systemViral hepatitisLiver diseaseLarge lymphHepatic lymphatic vesselsDiseased liverHepatocellular carcinomaLymphatic endothelial cellsEndothelial cellsLiverLymphatic vesselsPotential roleSignificant increaseDiseaseCurrent knowledgeReview articleOrgansCirrhosisHepatitisLymphCarcinomaLymphatics
2017
Biology of portal hypertension
McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatology International 2017, 12: 11-23. PMID: 29075990, PMCID: PMC7090883, DOI: 10.1007/s12072-017-9826-x.BooksMeSH KeywordsAnimalsAscitesBlood PlateletsEndothelial CellsEsophageal and Gastric VaricesFibrosisGastrointestinal HemorrhageHepatic EncephalopathyHepatic Veno-Occlusive DiseaseHepatorenal SyndromeHumansHypertension, PortalLiverMiceMicrovesselsModels, AnimalNeovascularization, PathologicRenal InsufficiencySplanchnic CirculationThrombosisVascular ResistanceConceptsLiver sinusoidal endothelial cellsPortal hypertensionMicrovascular thrombosisHepatic stellate cell activationHyperdynamic circulatory syndromeSystemic arterial vasodilationChronic liver diseaseIntrahepatic vascular resistanceSinusoidal portal hypertensionPortal hypertension resultsStellate cell activationSinusoidal endothelial cellsVascular biology researchHepatorenal syndromeGastroesophageal varicesVariceal hemorrhageVascular resistanceArterial vasodilationCirculatory syndromeRenal failureHepatic encephalopathyHypertension resultsLiver diseasePortosystemic shuntMesenteric vasculature
2015
Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase
Iwakiri Y. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase. Clinical And Molecular Hepatology 2015, 21: 319-325. PMID: 26770919, PMCID: PMC4712158, DOI: 10.3350/cmh.2015.21.4.319.Books
2014
Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions
Iwakiri Y, Shah V, Rockey DC. Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions. Journal Of Hepatology 2014, 61: 912-924. PMID: 24911462, PMCID: PMC4346093, DOI: 10.1016/j.jhep.2014.05.047.BooksConceptsChronic liver diseasePortal hypertensionLiver diseaseLiver fibrosis/cirrhosisVascular cellsMesenteric vascular circulationFibrosis/cirrhosisDynamic vascular changesCollateral vessel formationHepatic stellate cellsSinusoidal endothelial cellsGrowth factor pathwaysGrowth factor βExtrahepatic circulationExtrahepatic vasculatureArterial vasodilationLiver injuryVascular changesVasoactive peptidesHypertensionVascular pathobiologySystemic circulationStellate cellsVascular processesLiver vasculaturePathophysiology of Portal Hypertension
Iwakiri Y. Pathophysiology of Portal Hypertension. Clinics In Liver Disease 2014, 18: 281-291. PMID: 24679494, PMCID: PMC3971388, DOI: 10.1016/j.cld.2013.12.001.BooksConceptsPortal hypertensionBlood flowHyperdynamic circulatory syndromeIntrahepatic vascular resistancePortal blood flowVascular resistanceArterial vasodilationCirculatory syndromeEsophageal varicesLiver cirrhosisMajor complicationsLiver diseaseCollateral vesselsPortal circulationSystemic circulationHypertensionPathologic conditionsClinical researchCirrhosisVaricesVasodilationAscitesComplicationsPathophysiologySyndrome
2013
eNOS-derived nitric oxide regulates endothelial barrier function through VE-cadherin and Rho GTPases
Di Lorenzo A, Lin MI, Murata T, Landskroner-Eiger S, Schleicher M, Kothiya M, Iwakiri Y, Yu J, Huang PL, Sessa WC. eNOS-derived nitric oxide regulates endothelial barrier function through VE-cadherin and Rho GTPases. Journal Of Cell Science 2013, 126: 5541-5552. PMID: 24046447, PMCID: PMC3860306, DOI: 10.1242/jcs.115972.Peer-Reviewed Original ResearchMeSH KeywordsAdherens JunctionsAnimalsAntigens, CDCadherinsCapillary PermeabilityCells, CulturedCSK Tyrosine-Protein KinaseEndothelial CellsEndothelium, VascularGuanine Nucleotide Exchange FactorsHumansMaleMiceMice, Inbred C57BLMice, KnockoutNitric OxideNitric Oxide Synthase Type IIIPhosphorylationProtein Processing, Post-TranslationalProtein TransportSrc-Family KinasesStress FibersT-Lymphoma Invasion and Metastasis-inducing Protein 1Vascular Endothelial Growth Factor AConceptsAdherens junctionsVE-cadherinExchange factor Tiam1Vascular endothelial growth factorStress fiber formationEndothelial NO synthaseEndothelial adherens junctionsVE-cadherin phosphorylationCytoskeletal architectureRho GTPasesCortical actinCytoskeletal remodelingRac GTPaseC-SrcRac guanineRho activationMolecular mechanismsPhysiological roleEndothelial barrier functionFiber formationENOS activationGrowth factorEnhanced activationActivationNitric oxide
2012
Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO
Sangwung P, Greco TM, Wang Y, Ischiropoulos H, Sessa WC, Iwakiri Y. Proteomic Identification of S-Nitrosylated Golgi Proteins: New Insights into Endothelial Cell Regulation by eNOS-Derived NO. PLOS ONE 2012, 7: e31564. PMID: 22363674, PMCID: PMC3283662, DOI: 10.1371/journal.pone.0031564.Peer-Reviewed Original ResearchConceptsGolgi proteinsGolgi phosphoprotein 3S-nitrosylationGolgi apparatusCysteine residuesSelective S-nitrosylationPlasma membrane caveolaeGolgi/endoplasmic reticulumProtein S-nitrosylationTarget cysteine residuesEndothelial cellsEndothelial nitric oxide synthaseMembrane caveolaeEndothelial cell lysatesProteomic identificationEndothelial cell regulationGolgi membranesBiotin switchCell regulationEndoplasmic reticulumENOS stimulationCell lysatesProteinImmunoprecipitationWestern blot
2011
Endothelial dysfunction in the regulation of cirrhosis and portal hypertension
Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver International 2011, 32: 199-213. PMID: 21745318, PMCID: PMC3676636, DOI: 10.1111/j.1478-3231.2011.02579.x.BooksConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial dysfunctionArterial vasodilationPortosystemic collateral vesselsProduction of vasodilatorsDevelopment of cirrhosisCollateral vessel formationPathological vascular eventsSinusoidal endothelial cellsExtrahepatic circulationIntrahepatic resistanceOesophageal varicesVascular eventsVascular resistanceVasodilator moleculeCollateral vesselsSinusoidal microcirculationPortal veinHypertensionSystemic circulationBlood flowCirrhosisDysfunctionNitric oxideS-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO
Iwakiri Y. S-nitrosylation of proteins: A new insight into endothelial cell function regulated by eNOS-derived NO. Nitric Oxide 2011, 25: 95-101. PMID: 21554971, PMCID: PMC3152628, DOI: 10.1016/j.niox.2011.04.014.BooksConceptsS-nitrosylationCellular processesGolgi apparatusIntracellular membrane domainPlasma membrane caveolaeEndothelial cell functionCell functionProtein traffickingMembrane caveolaeMembrane domainsCytoplasmic faceTarget proteinsCell cycleSignaling mechanismMessenger moleculesCell growthRedox stateProteinNitric oxide synthaseIntracellular reactionsNew insightsEndothelial NOSNitric oxideEndothelial nitric oxide synthaseFamily members
2007
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WC. Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease. Cell Metabolism 2007, 6: 446-457. PMID: 18054314, PMCID: PMC3621848, DOI: 10.1016/j.cmet.2007.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAnimalsApolipoproteins EApoptosisAtherosclerosisBone Marrow TransplantationCoronary OcclusionDisease Models, AnimalEndothelial CellsFemaleHumansInflammation MediatorsMacrophagesMaleMiceMice, KnockoutNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktConceptsLoss of Akt1Apolipoprotein E knockout backgroundOcclusive coronary artery diseaseBone marrow transfer experimentsAcute coronary syndromeCoronary artery diseaseLesion expansionCoronary syndromeCoronary atherosclerosisSevere atherosclerosisArtery diseaseInflammatory mediatorsCoronary lesionsVascular protectionVascular originProinflammatory genesENOS phosphorylationCardiovascular systemLesion formationGenetic ablationEndothelial cellsAtherogenesisEnhanced expressionKnockout backgroundVessel wallVascular endothelial dysfunction in cirrhosis
Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. Journal Of Hepatology 2007, 46: 927-934. PMID: 17391799, DOI: 10.1016/j.jhep.2007.02.006.BooksConceptsEndothelium-dependent relaxationEndothelial dysfunctionSinusoidal endothelial cellsPortal hypertensionVascular nitric oxide levelsVascular endothelial dysfunctionNitric oxide levelsSEC dysfunctionVascular resistanceEarly key eventSplanchnic circulationLiver cirrhosisVasodilator moleculeLiver microcirculationSystemic circulationOxide levelsCirrhosisDysfunctionEndothelial cellsHypertensionMultiple diseasesKey eventsArteryMicrocirculationDisease