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 ResearchConceptsLiver 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
2024
Chapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease
Iwakiri Y. Chapter 13 Liver Sinusoidal Cells in alcohol-associated liver disease. 2024, 285-291. DOI: 10.1016/b978-0-323-95262-0.00013-9.Peer-Reviewed Original ResearchAlcohol-associated liver diseaseLiver sinusoidal endothelial cellsPathogenesis of alcohol-associated liver diseaseChronic alcohol consumptionSinusoidal endothelial cellsLiver diseaseNormal function of immune cellsEndothelial cellsFunction of immune cellsSinusoidal cellsAlcohol consumptionIntrahepatic vascular toneHepatic stellate cellsEndothelial cell populationLiver sinusoidal cellsLiver cell typesImmune cellsAntigen clearanceVascular toneKupffer cells/macrophagesKupffer cellsStellate cellsCell populationsLiver homeostasisLiver
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
2021
Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases
Kondo R, Kawaguchi N, McConnell MJ, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Sun Z, Utsumi T, Strazzabosco M, Iwakiri Y. Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases. Hepatology Research 2021, 51: 1000-1006. PMID: 34260803, PMCID: PMC8444906, DOI: 10.1111/hepr.13696.Peer-Reviewed Original ResearchCOVID-19 patientsVon Willebrand factorLiver injuryPatient's liverPapa Giovanni XXIII HospitalHigher serum ALTLiver sinusoidal endothelial cellsLiver biopsy samplesSinusoidal endothelial cellsSinusoidal thrombosisSerum ALTAST levelsPathological characteristicsHigher fibrinogenPlatelet microthrombiBiopsy samplesMultiple organsPatientsDisease severityCoronavirus diseaseLiverEndothelial cellsInjurySecondary damageWillebrand factorPortal hypertension in cirrhosis: Pathophysiological mechanisms and therapy
Iwakiri Y, Trebicka J. Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy. JHEP Reports 2021, 3: 100316. PMID: 34337369, PMCID: PMC8318926, DOI: 10.1016/j.jhepr.2021.100316.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsHepatic stellate cellsPortal hypertensionChronic liver diseaseIntrahepatic vascular resistanceSinusoidal endothelial cellsExtrahepatic vasculatureVascular resistanceMicrovascular thrombosisHaemodynamic changesLiver diseasePathophysiological mechanismsPortal veinHypertensionPreclinical studiesEffective treatmentStellate cellsPathogenic complexityExtrahepatic mechanismsClinical advancesEffective therapeuticsUnsuccessful translationEndothelial cellsCirrhosisDysregulation
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
2016
Cellular distribution of injected PLGA-nanoparticles in the liver
Park JK, Utsumi T, Seo YE, Deng Y, Satoh A, Saltzman WM, Iwakiri Y. Cellular distribution of injected PLGA-nanoparticles in the liver. Nanomedicine Nanotechnology Biology And Medicine 2016, 12: 1365-1374. PMID: 26961463, PMCID: PMC4889500, DOI: 10.1016/j.nano.2016.01.013.Peer-Reviewed Original ResearchConceptsPLGA nanoparticlesSafety of nanoparticlesUptake of nanoparticlesNanoparticle deliveryLiver sinusoidal endothelial cellsNanoparticle retentionNanoparticlesHepatic stellate cellsSinusoidal endothelial cellsKupffer cellsStellate cellsEndothelial cellsTarget cell typeCell typesClodronate liposomesLiver therapyLiver cellsMajor cellsLiverCell populationsCellular distributionLiposomesCellsHepatocytes
2015
Nitric oxide in liver diseases
Iwakiri Y, Kim MY. Nitric oxide in liver diseases. Trends In Pharmacological Sciences 2015, 36: 524-536. PMID: 26027855, PMCID: PMC4532625, DOI: 10.1016/j.tips.2015.05.001.BooksConceptsLiver sinusoidal endothelial cellsEndothelial NO synthaseLiver diseaseNitric oxideSinusoidal endothelial cellsInducible NOSNO synthaseEndothelial cellsPathological processesDiseaseDisease developmentLiverFatty acidsS-guanylationComplicated rolePathophysiologyPathogenesisNOSProgressionImportant role
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 vasculature
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 oxide
2007
Vascular 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