Featured Publications
Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis
McConnell MJ, Kondo R, Kawaguchi N, Iwakiri Y. Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis. Hepatology Communications 2022, 6: 255-269. PMID: 34658172, PMCID: PMC8652692, DOI: 10.1002/hep4.1843.Peer-Reviewed Original ResearchMeSH KeywordsBlood Platelet DisordersCOVID-19Endothelium, VascularHumansInflammationLiver DiseasesThrombosisConceptsLiver injurySARS-CoV-2Severe acute respiratory syndrome coronavirus 2Coronavirus disease 2019 (COVID-19) symptomsAcute respiratory syndrome coronavirus 2Alcohol-related liver diseaseSARS-CoV-2 infectionRespiratory syndrome coronavirus 2Chronic liver failureLiver-related complicationsDirect viral infectionElevated aspartate aminotransferaseSyndrome coronavirus 2COVID-19Pathophysiologic explanationLiver failureLiver diseasePlatelet dysfunctionVascular inflammationInflammatory environmentHepatic effectsAlanine aminotransferaseViral infectionAspartate aminotransferaseHepatic foci
2015
Development of Small Diameter Nanofiber Tissue Engineered Arterial Grafts
Kurobe H, Maxfield MW, Tara S, Rocco KA, Bagi PS, Yi T, Udelsman B, Zhuang ZW, Cleary M, Iwakiri Y, Breuer CK, Shinoka T. Development of Small Diameter Nanofiber Tissue Engineered Arterial Grafts. PLOS ONE 2015, 10: e0120328. PMID: 25830942, PMCID: PMC4382213, DOI: 10.1371/journal.pone.0120328.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsSmall-diameter arteriesSynthetic graftsDiameter arteriesSurvival of miceLarge-sized arteriesF4/80-positive macrophagesInner luminal diameterMatrix metalloproteinases 2Smooth muscle actinAneurysmal dilatationGraft stenosisSurgical repairPatency ratesSham groupArterial graftsSized arteriesVascular diseaseSham operationBg miceLuminal diameterDoppler ultrasoundHistologic analysisInterposition conduitsMuscle actin
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 oxide
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 AgentsDecreased intrahepatic response to α1‐adrenergic agonists in lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function
Lee C, Loureiro‐Silva M, Abraldes JG, Iwakiri Y, Haq O, Groszmann RJ. Decreased intrahepatic response to α1‐adrenergic agonists in lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function. Journal Of Gastroenterology And Hepatology 2007, 22: 893-900. PMID: 17498219, DOI: 10.1111/j.1440-1746.2007.04922.x.Peer-Reviewed Original ResearchConceptsLipopolysaccharide-treated ratsKupffer cell functionVascular responsesAdrenergic agonistsKupffer cellsNormal liverSinusoidal areaNitric oxide synthase inhibitorCell functionOxide synthase inhibitorRole of KupfferVascular tone controlNitric oxide overproductionKrebs-Henseleit solutionNitric oxide productionΑ1-adrenergic agonistDose-response curveIntrahepatic responseMicrovascular abnormalitiesSecond doseEndotoxemic ratsLiver perfusionSynthase inhibitorMethoxamineGadolinium chlorideVascular 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
2005
Akt1/protein kinase Bα is critical for ischemic and VEGF-mediated angiogenesis
Ackah E, Yu J, Zoellner S, Iwakiri Y, Skurk C, Shibata R, Ouchi N, Easton RM, Galasso G, Birnbaum MJ, Walsh K, Sessa WC. Akt1/protein kinase Bα is critical for ischemic and VEGF-mediated angiogenesis. Journal Of Clinical Investigation 2005, 115: 2119-2127. PMID: 16075056, PMCID: PMC1180542, DOI: 10.1172/jci24726.Peer-Reviewed Original ResearchConceptsSerine-threonine protein kinaseAkt1/protein kinase BαProtein kinase BαProtein kinase BAkt1-/- miceIndividual Akt isoformsLoss of Akt1Substrate phosphorylationCellular functionsAkt substrateProtein kinaseAkt isoformsAkt1 knockout miceGene expressionGenetic lossKinase BBasal phosphorylationCell metabolismPostnatal angiogenesisCellular migrationVivo roleCell migrationAKT1Essential rolePhosphorylation
2004
Targeting of Endothelial Nitric-oxide Synthase to the Cytoplasmic Face of the Golgi Complex or Plasma Membrane Regulates Akt- Versus Calcium-dependent Mechanisms for Nitric Oxide Release*
Fulton D, Babbitt R, Zoellner S, Fontana J, Acevedo L, McCabe TJ, Iwakiri Y, Sessa WC. Targeting of Endothelial Nitric-oxide Synthase to the Cytoplasmic Face of the Golgi Complex or Plasma Membrane Regulates Akt- Versus Calcium-dependent Mechanisms for Nitric Oxide Release*. Journal Of Biological Chemistry 2004, 279: 30349-30357. PMID: 15136572, DOI: 10.1074/jbc.m402155200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalciumCalmodulinCell MembraneCOS CellsCysteineCytoplasmEndothelium, VascularGolgi ApparatusHumansMicroscopy, FluorescenceMyristic AcidsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPalmitic AcidsPhosphorylationProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSerineTransfectionUmbilical VeinsConceptsPlasma membraneGolgi complexAkt-dependent phosphorylationEndothelial nitricoxide synthasePool of enzymesCalcium-dependent activationCytoplasmic faceGolgi membranesENOS constructMembrane versionFusion proteinCytoplasmic aspectFunctional rolePhosphorylationENOS activationHeterogeneous localizationMembraneCalcium fluxCalcium-dependent mechanismSynthaseActivationEndothelial nitric oxide synthaseFurther activationComplexesNitricoxide synthase
2003
Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice
Gratton J, Lin MI, Yu J, Weiss ED, Jiang ZL, Fairchild TA, Iwakiri Y, Groszmann R, Claffey KP, Cheng Y, Sessa WC. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2003, 4: 31-39. PMID: 12892711, DOI: 10.1016/s1535-6108(03)00168-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillary PermeabilityCarcinoma, HepatocellularCarcinoma, Lewis LungCaveolin 1CaveolinsDisease ProgressionEndothelium, VascularEnzyme InhibitorsLiver Neoplasms, ExperimentalLung NeoplasmsMaleMiceMice, Inbred C57BLMice, KnockoutMice, NudeNeovascularization, PhysiologicNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPeptide FragmentsVascular Endothelial Growth Factor AConceptsEndothelial nitric oxide synthaseTumor progressionAntitumor actionDelays tumor progressionENOS knockout miceNitric oxide synthaseTumor blood vesselsTumor microvascular permeabilityOxide synthaseMicrovascular permeabilityKnockout miceAntiangiogenic effectsTumor vasculatureCell-permeable peptideMicrovascular hyperpermeabilityNovel targetNormal vasculatureHyperpermeabilityBlood vesselsCavtratinAntitumor therapyProgressionMiceSelective inhibitionVasculature