2023
The evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammation
2021
Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjuryAlcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90
2020
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 ResearchMeSH KeywordsAnimalsCapillariesCarbon TetrachlorideEndothelial CellsGene Expression RegulationLiver CirrhosisMiceSingle-Cell AnalysisTranscriptomeConceptsLiver 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
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 vasculature