2021
Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH
Maeda H, Ishima Y, Saruwatari J, Mizuta Y, Minayoshi Y, Ichimizu S, Yanagisawa H, Nagasaki T, Yasuda K, Oshiro S, Taura M, McConnell MJ, Oniki K, Sonoda K, Wakayama T, Kinoshita M, Shuto T, Kai H, Tanaka M, Sasaki Y, Iwakiri Y, Otagiri M, Watanabe H, Maruyama T. Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH. Journal Of Controlled Release 2021, 341: 457-474. PMID: 34856227, DOI: 10.1016/j.jconrel.2021.11.039.Peer-Reviewed Original ResearchConceptsMannose receptor C type 1Treatment of NASHNonalcoholic steatohepatitisKupffer cellsBlood flowNO donorReactive oxygen speciesHepatic blood flowDevelopment of steatohepatitisNASH model miceC type 1Nitric oxide donorOxidative stress-associated pathologiesStress-associated pathologiesCombination therapyHepatoprotective effectModel miceLiver lobeOxide donorType 2Therapeutic potentialType 1Nitric oxidePathological phenotypesSpecific uptake
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.BooksNitric 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
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
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
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
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 Agents[214] NITRIC OXIDE IS A MEDIATOR OF THE ADENOSINE-INDUCED VASODILATATION OF THE HEPATIC ARTERY IN CCL-CIRRHOTIC RATS
Zipprich A, Iwakiri Y, Ripoll C, Loureiro-Silva M. [214] NITRIC OXIDE IS A MEDIATOR OF THE ADENOSINE-INDUCED VASODILATATION OF THE HEPATIC ARTERY IN CCL-CIRRHOTIC RATS. Journal Of Hepatology 2007, 46: s89. DOI: 10.1016/s0168-8278(07)61812-1.Peer-Reviewed Original Research
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 synthaseIncreased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers
Loureiro-Silva MR, Iwakiri Y, Abraldes JG, Haq O, Groszmann RJ. Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. Journal Of Hepatology 2006, 44: 886-893. PMID: 16545481, DOI: 10.1016/j.jhep.2006.01.032.Peer-Reviewed Original ResearchMeSH Keywords3',5'-Cyclic-GMP PhosphodiesterasesAnimalsCyclic Nucleotide Phosphodiesterases, Type 5Enzyme InhibitorsLiver CirculationLiver CirrhosisMaleNitric OxideNitric Oxide SynthaseOmega-N-MethylargininePhosphodiesterase InhibitorsPhosphoric Diester HydrolasesPiperazinesPurinesRatsRats, Sprague-DawleySildenafil CitrateSulfonesVasodilationConceptsPDE-5 expressionPhosphodiesterase-5 expressionCirrhotic liverCirrhotic rat liverPresence of sildenafilNitric oxideVasodilator responseDeficient responseNormal liverAscitic cirrhotic ratsDecreased vascular responseDecreased vasodilator responseConcentration-response curvesRat liverCyclic guanosine 3Second messenger cyclic guanosine 3Vasodilator effectCirrhotic ratsVascular responsesBACKGROUND/Liver perfusionDecreased responseSpontaneous NO donorSildenafil citrateNO donorThe 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
2004
The paradox: vasoconstriction and vasodilation
Iwakiri Y, Groszmann R. The paradox: vasoconstriction and vasodilation. 2004, 57-67. DOI: 10.1007/978-94-007-1042-9_7.Peer-Reviewed Original ResearchPortal hypertensionLiver diseaseVascular toneNitric oxideHyperdynamic circulatory syndromeChronic liver diseaseHomeostatic mechanismsBody's homeostatic mechanismsCirculatory syndromeImpaired oxygenationElectrolyte imbalanceHomeostatic functionsKey moleculesHypertensionProgressive alterationDiseaseToneVasoconstrictionVasodilationPatientsPatients1Major rolePathogenesisSyndromeAbnormalities
2003
Neuronal nitric oxide synthase(NNOS) is upregulated in superior mesenteric arteries in portal hypertensive rats
Kwon S, Iwakiri Y, Groszmann R. Neuronal nitric oxide synthase(NNOS) is upregulated in superior mesenteric arteries in portal hypertensive rats. Journal Of Hepatology 2003, 38: 62-63. DOI: 10.1016/s0168-8278(03)80613-x.Peer-Reviewed Original Research
2002
Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension
Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension. AJP Gastrointestinal And Liver Physiology 2002, 283: g1074-g1081. PMID: 12381520, DOI: 10.1152/ajpgi.00145.2002.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationEndothelial NO synthaseHyperdynamic circulatory statePortal hypertensive animalsHyperdynamic circulationPortal hypertensionCirculatory stateHypertensive animalsInducible NOSNitric oxideLevels of vasodilatorsPortal vein ligationSham-operated groupSham-operated animalsSystemic vasodilationSplanchnic circulationPeripheral resistanceVein ligationSham animalsNO synthaseKnockout miceGene deletionINOS geneHemodynamic characteristicsMice