2024
Endothelial TGF-β Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease
Zhang W, Gonzalez L, Li X, Bai H, Li Z, Taniguchi R, Langford J, Ohashi Y, Thaxton C, Aoyagi Y, Yatsula B, Martin K, Goodwin J, Tellides G, Long X, Shu C, Dardik A. Endothelial TGF-β Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 2509-2526. PMID: 39297205, PMCID: PMC11593991, DOI: 10.1161/atvbaha.124.320933.Peer-Reviewed Original ResearchChronic kidney diseaseTGF-b signalingArteriovenous fistula patencyArteriovenous fistulaKidney diseaseAVF patencyEndothelial cellsAssociated with endothelial injuryArteriovenous fistula diameterImprove AVF patencyIncreased outward remodelingReduced patencyInduced endothelial-to-mesenchymal transitionAortocaval fistula modelSmooth muscle cell proliferationArteriovenous fistula failureAttenuated EndMTEnd-stage kidney diseaseHuman arteriovenous fistulaeSmooth muscle cellsMuscle cell proliferationEndothelial-to-mesenchymal transitionMouse endothelial cellsInhibition of EndMTEndothelial-mesenchymal transition
2023
A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells
Li X, Jiang Q, Song G, Barkestani M, Wang Q, Wang S, Fan M, Fang C, Jiang B, Johnson J, Geirsson A, Tellides G, Pober J, Jane-wit D. A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature Communications 2023, 14: 3002. PMID: 37225719, PMCID: PMC10209169, DOI: 10.1038/s41467-023-38684-2.Peer-Reviewed Original ResearchConceptsEndothelial cellsInflammasome activityMembrane attack complexCaspase-1Potential therapeutic targetChronic rejectionComplement membrane attack complexTissue inflammationNLRP3 inflammasomeTissue injuryMouse modelTherapeutic targetDependent mannerInflammationAttack complexInflammasomeHuman tissuesFlightless IInhibitory associationsSkin modelRNF34CellsGenetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Lee S, Schleer H, Park H, Jang E, Boyer M, Tao B, Gamez-Mendez A, Singh A, Folta-Stogniew E, Zhang X, Qin L, Xiao X, Xu L, Zhang J, Hu X, Pashos E, Tellides G, Shaul P, Lee W, Fernandez-Hernando C, Eichmann A, Sessa W. Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2023, 2: 438-448. PMID: 39196046, PMCID: PMC11358031, DOI: 10.1038/s44161-023-00266-2.Peer-Reviewed Original ResearchLDL transcytosisLDL receptor knockout miceReceptor knockout miceAtherosclerotic cardiovascular diseaseLow-density lipoprotein accumulationHigh-fat dietPromising therapeutic strategyTherapeutic neutralizationMacrophage infiltrationTriglyceride levelsLDL entryCardiovascular diseaseSelective monoclonal antibodiesLipoprotein accumulationTherapeutic strategiesKnockout micePlaque formationAtherosclerosis initiationType 1Genetic deletionArterial wallMonoclonal antibodiesEndothelial cellsLDL accumulationMiceHedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells
Jiang B, Wang S, Song G, Jiang Q, Fan M, Fang C, Li X, Soh C, Manes T, Cheru N, Qin L, Ren P, Jortner B, Wang Q, Quaranta E, Yoo P, Geirsson A, Davis R, Tellides G, Pober J, Jane-Wit D. Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells. Science Signaling 2023, 16: eabo3406. PMID: 36943921, PMCID: PMC10061549, DOI: 10.1126/scisignal.abo3406.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryChronic vascular inflammationT cellsNLRP3 inflammasomeVascular inflammationChronic inflammationEndothelial cellsIFN-γ responsesControl T cellsNLRP3 inflammasome activityT memory cellsAllograft vasculopathyVascular sequelaeHuman endothelial cellsCoronary arteryEffector responsesCell-autonomous roleInflammasome activityMouse modelInflammationPatient samplesVigorous recruitmentInflammasomePrimary human cellsImmune signaling
2021
ZFYVE21 is a Mediator of Non-Canonical Hedgehog Signaling Activating NLRP3 Inflammasomes in a Pathologic Subset of CD4+PD-1hi T Cells
Jiang B, Fang C, Soh C, Li X, Geirsson A, Tellides G, Pober J, Jane-Wit D. ZFYVE21 is a Mediator of Non-Canonical Hedgehog Signaling Activating NLRP3 Inflammasomes in a Pathologic Subset of CD4+PD-1hi T Cells. The Journal Of Heart And Lung Transplantation 2021, 40: s136. DOI: 10.1016/j.healun.2021.01.422.Peer-Reviewed Original ResearchT cellsNLRP3 inflammasomeEndothelial cellsDelayed graft functionSubset of CD4Humanized mouse modelComplement-mediated injuryNLRP3 inflammasome activityHuman lymphoid cellsNon-canonical Hedgehog signallingNon-canonical hedgehogGraft functionPeripheral injuryMemory CD4Human endothelial cellsPD-1Injury showCellular immunityVascular injuryChemokine receptorsTissue injuryPrimary human endothelial cellsInflammasome activityMouse modelLymphoid cells
2019
ZFYVE21 is a Novel Complement-Induced Rab5 Effector Protein Mediating Cardiac Allograft Vasculopathy
Jane-Wit D, Fang C, Liu L, Qin L, Li G, Tellides G, Pober J. ZFYVE21 is a Novel Complement-Induced Rab5 Effector Protein Mediating Cardiac Allograft Vasculopathy. The Journal Of Heart And Lung Transplantation 2019, 38: s249. DOI: 10.1016/j.healun.2019.01.618.Peer-Reviewed Original ResearchCardiac allograft vasculopathyAllograft vasculopathyHumanized mouse modelMembrane attack complexNF-κB-inducing kinaseTransplant biopsiesMouse modelEC activationHuman coronary artery segmentsEndothelial cellsAntibody-mediated rejectionTransplant organ rejectionCoronary artery segmentsHuman lymphoid cellsVascular inflammationOrgan rejectionArtery segmentsPharmacologic alterationsVasculopathyLymphoid cellsNF-kBClinical relevance
2013
IDENTIFICATION OF A NOVEL COMPLEMENT–INDUCED SIGNALING PATHWAY IN ENDOTHELIAL CELLS THAT IS IMPLICATED IN THE DEVELOPMENT OF CORONARY GRAFT VASCULOPATHY
Jane–Wit D, Pober J, Tellides G. IDENTIFICATION OF A NOVEL COMPLEMENT–INDUCED SIGNALING PATHWAY IN ENDOTHELIAL CELLS THAT IS IMPLICATED IN THE DEVELOPMENT OF CORONARY GRAFT VASCULOPATHY. Journal Of The American College Of Cardiology 2013, 61: e2109. DOI: 10.1016/s0735-1097(13)62109-9.Peer-Reviewed Original Research
2001
HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1
Tereb D, Kirkiles-Smith N, Kim R, Wang Y, Rudic R, Schechner J, Lorber M, Bothwell A, Pober J, Tellides G. HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1. Transplantation 2001, 71: 1622-1630. PMID: 11435975, DOI: 10.1097/00007890-200106150-00023.Peer-Reviewed Original ResearchConceptsTumor necrosis factorHuman tumor necrosis factorArtery graftT cellsNecrosis factorPig coronary artery endothelial cellsHuman T-cell infiltrationVascular cell adhesion molecule-1Human peripheral blood mononuclearHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsHuman leukocytesEndothelial cellsMajor histocompatibility complex antigensCell adhesion molecule-1Graft endothelial cellsT-cell infiltratesBeige mouse modelCoronary artery endothelial cellsT cell infiltrationCoronary artery graftsBlood mononuclear cellsPeripheral blood mononuclearCoronary artery segmentsAdhesion molecule-1
2000
Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts
Kirkiles-Smith N, Tereb D, Kim R, McNiff J, Schechner J, Lorber M, Pober J, Tellides G. Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts. The Journal Of Immunology 2000, 164: 6601-6609. PMID: 10843720, DOI: 10.4049/jimmunol.164.12.6601.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAdultAnimalsCell Adhesion MoleculesDose-Response Relationship, ImmunologicDrug SynergismEndothelium, VascularGraft RejectionHistocompatibility AntigensHumansInterferon-gammaMiceMice, Inbred C57BLMice, SCIDMicrocirculationSevere Combined ImmunodeficiencySkin TransplantationSwineT-LymphocytesTransplantation, HeterologousTumor Necrosis Factor-alphaUp-RegulationConceptsHuman T-cell infiltrationPig skin xenograftsT cell infiltrationSkin xenograftsCell infiltrationHuman TNFIFN-gammaE-selectinT cell-mediated rejectionEndothelial cellsAdhesion moleculesCytokine-mediated injuryNonspecific inflammatory damagePig skin graftsCell-mediated rejectionAppropriate therapeutic targetsImmunodeficient mouse modelPorcine E-selectinEndothelial adhesion moleculesPorcine IFN-gammaClass II moleculesHuman skin allograftsMHC class IPorcine endothelial cellsImmunodeficient mouse hosts
1998
Transplantation Models in Human/Mouse Chimeras
Tellides G, Kirkiles N, Tereb D, Schechner J, Wilson J, Lorber M, Pober J. Transplantation Models in Human/Mouse Chimeras. 1998, 615-626. DOI: 10.1007/978-3-642-72140-3_63.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsSevere combined immunodeficiencyHuman/mouse chimerasTransplantation modelImmune responseB lymphocytesNatural killer cell activityMouse chimerasHuman peripheral blood mononuclear cellsEndothelial cellsKiller cell activityHuman peripheral blood leukocytesCellular immune responsesBlood mononuclear cellsHuman immune responsePeripheral blood leukocytesHuman mononuclear leukocytesPig endothelial cellsHuman allogeneicPig graftsArtery graftAdoptive transferNK cellsMononuclear cellsHost mice