Featured Publications
Single-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
2021
Portal 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
2020
Pathophysiology of Portal Hypertension
Iwakiri Y, Groszmann R. Pathophysiology of Portal Hypertension. 2020, 659-669. DOI: 10.1002/9781119436812.ch51.Peer-Reviewed Original ResearchPortal hypertensionGastroesophageal variceal hemorrhageHyperdynamic circulatory syndromeIntrahepatic portal hypertensionNew blood vessel formationPre-existing vascular bedExtrahepatic circulationVariceal hemorrhageCirculatory syndromeLiver cirrhosisLethal complicationVascular toneVascular bedHypertensionFrequent causeCell-specific modulationPlatelet activationBlood vessel formationOrgans/tissuesVasoconstrictor moleculesCirrhosisTherapeutic purposesVessel formationPathophysiologySubsequent development
2019
O-GlcNAc transferase suppresses necroptosis and liver fibrosis
Zhang B, Li MD, Yin R, Liu Y, Yang Y, Mitchell-Richards KA, Nam JH, Li R, Wang L, Iwakiri Y, Chung D, Robert ME, Ehrlich BE, Bennett AM, Yu J, Nathanson MH, Yang X. O-GlcNAc transferase suppresses necroptosis and liver fibrosis. JCI Insight 2019, 4: e127709. PMID: 31672932, PMCID: PMC6948774, DOI: 10.1172/jci.insight.127709.Peer-Reviewed Original ResearchConceptsReceptor-interacting protein kinase 3Liver fibrosisLiver diseaseHepatocyte necroptosisEthanol-induced liver injuryAlcoholic liver cirrhosisChronic liver diseaseMultiple liver diseasesWeeks of ageProtein expression levelsPortal inflammationLiver cirrhosisLiver injuryBallooning degenerationElevated protein expression levelsSpontaneous genetic modelFibrosisKey suppressorKey mediatorMiceProtein kinase 3CirrhosisExpression levelsGlcNAc levelsMixed lineage kinase
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.BooksConceptsHepatic lymphatic systemLymphatic systemViral hepatitisLiver diseaseLarge lymphHepatic lymphatic vesselsDiseased liverHepatocellular carcinomaLymphatic endothelial cellsEndothelial cellsLiverLymphatic vesselsPotential roleSignificant increaseDiseaseCurrent knowledgeReview articleOrgansCirrhosisHepatitisLymphCarcinomaLymphatics
2017
Corrigendum to “Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension” [J Hepatol 62 (2015) 325–331]
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed FEZ, Davies N, Sharma V, Iwakiri Y, Jalan R. Corrigendum to “Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension” [J Hepatol 62 (2015) 325–331]. Journal Of Hepatology 2017, 67: 1124. PMID: 28893453, DOI: 10.1016/j.jhep.2017.08.004.Peer-Reviewed Original Research
2014
Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension
Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed Fel Z, Davies N, Sharma V, Iwakiri Y, Jalan R. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. Journal Of Hepatology 2014, 62: 325-331. PMID: 25152204, PMCID: PMC4530584, DOI: 10.1016/j.jhep.2014.08.024.Peer-Reviewed Original ResearchConceptsDDAH-1 expressionMean arterial pressurePortal hypertensionENOS activityDDAH-1Farnesoid X receptor (FXR) agonismFXR agonist obeticholic acidPortal pressure reductionAgonist obeticholic acidPortal pressure measurementsHealthy liver tissueArterial pressureENOS inhibitorHuman cirrhosisBDL ratsObeticholic acidSpecific molecular targetsPlasma ALTReceptor agonismSaline controlsCirrhosisCirrhosis ratsHypertensionOA treatmentTranslational studiesPathophysiology 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
The lymphatic vascular system in liver diseases: its role in ascites formation
Chung C, Iwakiri Y. The lymphatic vascular system in liver diseases: its role in ascites formation. Clinical And Molecular Hepatology 2013, 19: 99-104. PMID: 23837133, PMCID: PMC3701854, DOI: 10.3350/cmh.2013.19.2.99.BooksConceptsLiver fibrosis/cirrhosisFibrosis/cirrhosisLiver diseasePortal hypertensionAscites formationVascular systemLymphatic vascular systemNormal vascular functionPotential therapeutic targetVascular functionLiver tumorsTherapeutic targetDiseaseLymphatic systemTumor metastasisCirrhosisHypertensionLymphatic vesselsCirculatory systemPathogenesisLymphangiogenesisMetastasisTumorsLiverRole
2012
Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure
Huang H, Haq O, Utsumi T, Sethasine S, Abraldes JG, Groszmann RJ, Iwakiri Y. Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure. Journal Of Cellular And Molecular Medicine 2012, 16: 1125-1133. PMID: 21801303, PMCID: PMC3213314, DOI: 10.1111/j.1582-4934.2011.01399.x.Peer-Reviewed Original ResearchConceptsPlasma VEGF levelsPortal pressureVEGF levelsPortal hypertensionIntestinal VEGFDevelopment of cirrhosisFibrosis/cirrhosisAge-matched controlsGroups of ratsEnd of exposureCirrhosisRatsSignificant positive correlationWeeksHypertensionVEGFInhalationPositive correlationDifferent stagesCarbon tetrachlorideLevelsPathologyControl
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
2010
The Systemic and Splanchnic Circulations
Iwakiri Y. The Systemic and Splanchnic Circulations. Clinical Gastroenterology 2010, 305-321. DOI: 10.1007/978-1-60761-866-9_15.Peer-Reviewed Original ResearchPortal hypertensionArterial vasodilatationSplanchnic circulationSystemic circulationNitric oxideInitiation of vasodilatationSystemic hemodynamic abnormalitiesDevelopment of complicationsSplanchnic blood flowProgressive vasodilatationHemodynamic abnormalitiesIntestinal microcirculationLiver cirrhosisLiver diseaseVasodilator moleculeHypertensionVasodilatationBlood flowCirrhosisPatientsMolecular mechanismsKey eventsSensory mechanismsCirculationComplications
2008
Vascular biology and pathobiology of the liver: Report of a single‐topic symposium
Iwakiri Y, Grisham M, Shah V. Vascular biology and pathobiology of the liver: Report of a single‐topic symposium. Hepatology 2008, 47: 1754-1763. PMID: 18393322, PMCID: PMC2724750, DOI: 10.1002/hep.22203.BooksConceptsPortal hypertensionVascular biologyIschemia-reperfusion injurySingle Topic ConferenceMajority of morbidityClinical sequelaeIR injurySpecific disease syndromesLiver diseaseVascular syndromesVascular diseaseVascular cell signalingHypertensionDisease syndromeLiver cellsSyndromeMajor vascular defectsLiverVascular defectsInjuryDiseasePathobiologyAmerican AssociationCell signalingCirrhosis
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