2019
Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Zhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.Peer-Reviewed Original ResearchConceptsHigh-fat dietSignificant clinical applicabilityHuman nonalcoholic steatohepatitisNonalcoholic steatohepatitisOral digoxinLiver injuryCell subsetsPathway activationMouse modelHigh-fat diet mouse modelLiver injury mouse modelHepatocyte mitochondrial dysfunctionClinical applicabilityDiet mouse modelInjury mouse modelDifferential involvementLarge clinical experienceNLRP3 inflammasome activationSignificant protective effectHIF-1α transactivationHepatic oxidative stress responseHypoxia-inducible factorLiver inflammationHFD miceWide dosage range
2006
Increased 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 donor
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
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 characteristicsMicePhosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension
Iwakiri Y, Tsai MH, McCabe TJ, Gratton JP, Fulton D, Groszmann RJ, Sessa WC. Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension. AJP Heart And Circulatory Physiology 2002, 282: h2084-h2090. PMID: 12003815, DOI: 10.1152/ajpheart.00675.2001.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAndrostadienesAnimalsEnzyme InhibitorsHypertension, PortalLigationMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIOmega-N-MethylargininePhosphorylationPortal VeinProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyVasoconstrictor AgentsWortmanninConceptsEndothelial nitric oxide synthasePortal vein ligationPhosphorylation of eNOSMesenteric arterial bedPortal hypertensionPVL groupArterial bedNO productionMale Sprague-Dawley ratsEarly portal hypertensionMonomethyl-L-arginineNitric oxide synthaseSprague-Dawley ratsExcessive NO productionG protein-coupled receptorsVivo perfusion studiesPVL ratsProtein-coupled receptorsPerfusion pressureSham groupVein ligationENOS expressionOxide synthaseReduced responsivenessKinase/Akt pathway