Featured Publications
Hepatic lymphatic vascular system in health and disease
Jeong J, Tanaka M, Iwakiri Y. Hepatic lymphatic vascular system in health and disease. Journal Of Hepatology 2022, 77: 206-218. PMID: 35157960, PMCID: PMC9870070, DOI: 10.1016/j.jhep.2022.01.025.Peer-Reviewed Original ResearchConceptsLiver diseaseNon-alcoholic fatty liver diseaseLymphatic systemFatty liver diseaseCongenital liver diseasesPotential therapeutic strategyHepatic lymphatic systemLiver transplantationPortal hypertensionMalignant tumorsTherapeutic strategiesDisease pathogenesisHepatic physiologyDiseasePathological conditionsSpecific markersLymphatic vesselsVascular systemLymphatic vascular systemOrgansTissue homeostasisHypertensionTransplantationPathophysiologyPathogenesis
2023
Lymphatic drainage dysfunction is related to clinically significant portal hypertension
Ma R, Iwakiri Y. Lymphatic drainage dysfunction is related to clinically significant portal hypertension. Hepatology International 2023, 17: 1327-1330. PMID: 37743398, DOI: 10.1007/s12072-023-10592-z.Peer-Reviewed Original Research
2018
Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats
Saruwatari J, Dong C, Utsumi T, Tanaka M, McConnell M, Iwakiri Y. Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats. Scientific Reports 2018, 8: 17983. PMID: 30573742, PMCID: PMC6301948, DOI: 10.1038/s41598-018-36297-0.Peer-Reviewed Original ResearchConceptsCell proliferationWhole-genome microarray analysisInterferon-mediated antiviral activitySuppression of genesMicroRNA-mRNA networkSignificant differential expressionPotential biological functionsMRNA expression profilesTarget mRNAsBiological functionsExpression profilesMicroarray analysisDifferential expressionInnate immune responseMicroRNAsCellular mechanismsHematopoietic systemIntegrated analysisGenesNew insightsComprehensive profileMRNAProliferationTissue fibrosisImportant role
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 vasculatureThe portal hypertension syndrome: etiology, classification, relevance, and animal models
Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatology International 2017, 12: 1-10. PMID: 29064029, DOI: 10.1007/s12072-017-9827-9.BooksMeSH KeywordsAdrenergic beta-AntagonistsAnimalsAscitesCarcinoma, HepatocellularEarly Detection of CancerEsophageal and Gastric VaricesGastrointestinal HemorrhageHealthy LifestyleHemorrhageHepatic EncephalopathyHepatic VeinsHumansHypertension, PortalHypolipidemic AgentsLigationLiver CirrhosisLiver NeoplasmsModels, AnimalPrognosisSimvastatinConceptsHepatic vein pressure gradientNon-bleeding complicationsPortal hypertensionLiver transplantationDisease stagePortal hypertension syndromeAccurate risk stratificationDevelopment of varicesEndoscopic band ligationAim of treatmentPresent day therapyHealthy life styleBackgroundPortal hypertensionDecompensated patientsHVPG responseRefractory ascitesVariceal bleedingClinical decompensationLarge varicesBand ligationDay therapyHepatic encephalopathyBetter prognosisRisk stratificationEtiologic treatment
2015
Can hypersplenism secondary to portal hypertension be treated by non-selective beta blockers?
Kim MY, Iwakiri Y. Can hypersplenism secondary to portal hypertension be treated by non-selective beta blockers? Hepatology International 2015, 9: 337-338. PMID: 25788189, PMCID: PMC5046185, DOI: 10.1007/s12072-014-9601-1.Commentaries, Editorials and Letters
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 studiesVascular 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
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.BooksMeSH KeywordsAscitesHumansHypertension, PortalLiver CirrhosisLiver DiseasesLiver NeoplasmsLymphangiogenesisLymphatic VesselsConceptsLiver 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 oxideReticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis
Zhang D, Utsumi T, Huang H, Gao L, Sangwung P, Chung C, Shibao K, Okamoto K, Yamaguchi K, Groszmann RJ, Jozsef L, Hao Z, Sessa WC, Iwakiri Y. Reticulon 4B (Nogo‐B) is a novel regulator of hepatic fibrosis. Hepatology 2011, 53: 1306-1315. PMID: 21480333, PMCID: PMC3667398, DOI: 10.1002/hep.24200.Peer-Reviewed Original ResearchConceptsBile duct ligationLiver fibrosisPortal pressureKO micePortal hypertensionReticulon 4BWT mice 4 weeksMice 4 weeksFibrosis/cirrhosisSham-operated controlsB knockout miceHepatic stellate cellsPotential therapeutic targetHuman liver sectionsAbsence of NogoGrowth factor β stimulationMechanism of NogoTGFβ/SMAD2WT miceVascular injuryHepatic fibrosisSham operationCirrhotic liverDuct ligationStellate cells
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
The Molecules
Iwakiri Y. The Molecules. Journal Of Clinical Gastroenterology 2007, 41: s288-s294. PMID: 17975478, DOI: 10.1097/mcg.0b013e3181468b4c.BooksMeSH KeywordsAdrenomedullinAnimalsArteriesBiological FactorsCannabinoid Receptor ModulatorsCarbon MonoxideCoenzymesEndothelium, VascularEpoprostenolHumansHydrogen SulfideHypertension, PortalLiver CirrhosisNitric OxideNitric Oxide Synthase Type IIIPortal PressureSplanchnic CirculationTumor Necrosis Factor-alphaUp-RegulationVascular Endothelial Growth Factor AVasodilationVasodilator AgentsVascular 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
2006
Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. AJP Gastrointestinal And Liver Physiology 2006, 290: g980-g987. PMID: 16603731, DOI: 10.1152/ajpgi.00336.2005.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsEndothelium, VascularHypertension, PortalIndolesIntestinal MucosaIntestinesJejunumMaleMicrocirculationNeovascularization, PathologicNitric Oxide SynthaseNitric Oxide Synthase Type IIIPortal PressurePyrrolesRatsUp-RegulationVascular Endothelial Growth Factor AVasodilationConceptsEndothelial NO synthasePortal hypertensionPortal vein ligationHyperdynamic circulationPortal pressureENOS expressionMild increaseVEGF expressionUpregulates Vascular Endothelial Growth FactorNitric oxideEndothelial nitric oxide synthaseAdvanced portal hypertensionVascular endothelial growth factorNitric oxide synthaseEndothelial growth factorInhibition of VEGFHyperdynamic statePVL ratsSplanchnic hemodynamicsIntestinal microcirculationPortosystemic shuntingVein ligationSham ratsOxide synthaseNO synthaseThe hyperdynamic circulation of chronic liver diseases: From the patient to the molecule
Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: From the patient to the molecule. Hepatology 2006, 43: s121-s131. PMID: 16447289, DOI: 10.1002/hep.20993.BooksMeSH KeywordsAdrenomedullinAnimalsBiological FactorsBlood PressureCannabinoid Receptor ModulatorsCarbon MonoxideChronic DiseaseDisease Models, AnimalEndothelium, VascularHumansHydrogen SulfideHypertension, PortalLiverLiver DiseasesNitric OxidePeptidesSplanchnic CirculationTumor Necrosis Factor-alphaVasodilationConceptsHyperdynamic circulatory syndromeChronic liver diseaseCirculatory syndromeLiver diseaseVasodilator moleculeClinical observationsExperimental modelComplex pathophysiological mechanismsHyperdynamic circulationProgressive vasodilatationPortal hypertensionPathophysiological mechanismsVascular abnormalitiesComplex syndromeMultiple organsPatientsNitric oxideSyndromeVasodilatationDiseaseDetrimental effectsHypertensionAbnormalitiesComplex mechanisms
2003
A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats
Loureiro-Silva MR, Cadelina GW, Iwakiri Y, Groszmann RJ. A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. Journal Of Hepatology 2003, 39: 940-946. PMID: 14642609, DOI: 10.1016/j.jhep.2003.09.018.Peer-Reviewed Original ResearchConceptsBlood flow increasesCirrhotic ratsPortal pressureUrsodeoxycholic acidLiver perfusionFlow/pressure curvesNO donorAscitic cirrhotic ratsBlood volume expansionBasal heart rateSitu liver perfusionNitric oxide productionNitric oxide donorDose/response curveBlood flow measurementsPortal hypertensionHemodynamic effectsArterial pressureFlow increasesVascular responsesControl ratsBlood infusionBACKGROUND/Heart rateOxide donorMesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats
Tsai MH, Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003, 125: 1452-1461. PMID: 14598261, DOI: 10.1016/j.gastro.2003.07.014.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationSuperior mesenteric arterySMA vascular resistancePortal hypertensive ratsRAL ratsMesenteric vasoconstrictionPortal pressureVascular resistanceArterial pressureHypertensive ratsMesenteric arteryNitric oxide synthase activityNitric oxide synthase enzyme activitySMA blood flowMean arterial pressurePerfusion pressure changesPortal vein ligationENOS protein expressionSham-operated ratsOxide synthase activityMonomethyl-L-arginineNitric oxide overproductionEffects of vasoconstrictionRenal artery ligationENOS catalytic activity