2024
De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis—Brief Report
Ellis M, Riaz M, Huang Y, Anderson C, Hoareau M, Li X, Luo H, Lee S, Park J, Luo J, Batty L, Huang Q, Lopez C, Reinhardt D, Tellides G, Qyang Y. De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 1674-1682. PMID: 38752350, PMCID: PMC11209776, DOI: 10.1161/atvbaha.124.320790.Peer-Reviewed Original ResearchSupravalvular aortic stenosisVascular smooth muscle cellsSmooth muscle cellsMuscle cellsAortic stenosisMedial vascular smooth muscle cellsVascular proliferative diseasesEpigallocatechin gallate treatmentProliferative abnormalitiesPreclinical findingsHeart failureLuminal occlusionMouse modelCell hyperproliferationDefective elastinProliferative diseasesCardiovascular disordersFormation of elastinTherapeutic interventionsElastin assemblyElastin depositionStenosisMiceAortic mechanicsImproper formationMultiscale computational model of aortic remodeling following postnatal disruption of TGFβ signaling
Estrada A, Irons L, Tellides G, Humphrey J. Multiscale computational model of aortic remodeling following postnatal disruption of TGFβ signaling. Journal Of Biomechanics 2024, 169: 112152. PMID: 38763809, PMCID: PMC11141772, DOI: 10.1016/j.jbiomech.2024.112152.Peer-Reviewed Original ResearchAdult aortaTGFB signalingSmooth muscle cellsAortic remodelingCardiac-inducedMouse modelNormal mechanical loadingMuscle cellsPostnatal developmentHemodynamic loadNormal loadAortaMechanical homeostasisMechanical loadingMultiscale computational modelIncreasing loadLoadCell signalingGene productsStructural integrity
2023
Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsA 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 modelRNF34CellsFN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Chen M, Cavinato C, Hansen J, Tanaka K, Ren P, Hassab A, Li D, Youshao E, Tellides G, Iyengar R, Humphrey J, Schwartz M. FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43: e132-e150. PMID: 36994727, PMCID: PMC10133209, DOI: 10.1161/atvbaha.123.319120.Peer-Reviewed Original ResearchConceptsContractile gene expressionSmooth muscle cellsGene expressionMgR miceWild-type smooth muscle cellsMarfan miceAortic aneurysmMouse modelMarfan syndromeMouse aortic smooth muscle cellsPathogenesis of TAACytoplasmic domainVascular smooth muscle cellsThoracic aortic aneurysmAortic smooth muscle cellsCultured smooth muscle cellsNF-kB activationNF-kB inhibitionMolecular mechanismsIntegrin α2ECM remodelingElastic fiber integrityPhenotypic modulationMarfan's aneurysmsMgR/Hedgehog-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 signalingLonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome
Murtada S, Mikush N, Wang M, Ren P, Kawamura Y, Ramachandra A, Li D, Braddock D, Tellides G, Gordon L, Humphrey J. Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome. ELife 2023, 12: e82728. PMID: 36930696, PMCID: PMC10023154, DOI: 10.7554/elife.82728.Peer-Reviewed Original ResearchConceptsMouse modelLeft ventricular diastolic functionHutchinson-Gilford progeria syndromeVentricular diastolic functionPulse wave velocityDrug-associated effectsMTOR inhibitor rapamycinCardiovascular sequelaeDiastolic functionProgeria syndromeDevastating conditionCardiac functionCardiovascular functionClinical trialsCardiovascular diseaseMuscular arteriesUS FoodDrug AdministrationProgeria miceArterial structurePremature deathLonafarnibCardiovascular structureCharacteristics of agingInhibitor rapamycin
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 cellsAdventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFβ signaling
Kawamura Y, Murtada S, Gao F, Liu X, Tellides G, Humphrey J. Adventitial remodeling protects against aortic rupture following late smooth muscle-specific disruption of TGFβ signaling. Journal Of The Mechanical Behavior Of Biomedical Materials 2021, 116: 104264. PMID: 33508556, PMCID: PMC7959590, DOI: 10.1016/j.jmbbm.2020.104264.Peer-Reviewed Original ResearchConceptsAortic dissectionMouse modelAortic wallCompensatory changesThoracic aortic dissectionMuscle-specific disruptionSmooth muscle cellsLoss of TGFβMedial integrityAortic ruptureClinical presentationMuscle cellsQuantitative histologyMatrix turnoverTGFβ receptorsDissectionWall stressTGFβType IIndividual subjectsSpecific disruptionVivo valuesExaminationRupture
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
2018
Central artery stiffness and thoracic aortopathy
Humphrey J, Tellides G. Central artery stiffness and thoracic aortopathy. AJP Heart And Circulatory Physiology 2018, 316: h169-h182. PMID: 30412443, PMCID: PMC6880196, DOI: 10.1152/ajpheart.00205.2018.Peer-Reviewed Original ResearchConceptsCentral arteriesEnd-organ diseaseProximal thoracic aortaCentral artery stiffnessPrimary risk factorUncontrolled hypertensionAntihypertensive medicationsNonsurgical treatmentSignificant morbidityArtery stiffnessAortic aneurysmPulse pressureRisk factorsThoracic aortaDisease progressionStrenuous exerciseMouse modelMarfan syndromeWeight liftingGlobal hemodynamicsDysfunctional mechanosensingLethal conditionAortaGenetic mutationsArtery
2010
Graft-derived IL-6 Promotes Allogeneic T Cell Intimal Infiltration and Intimal Expansion in a Chimeric Mouse Model of Human Artery Rejection
Fogal B, Rao D, Yi T, Tellides G, Kulkarni S, Pober J. Graft-derived IL-6 Promotes Allogeneic T Cell Intimal Infiltration and Intimal Expansion in a Chimeric Mouse Model of Human Artery Rejection. Clinical Immunology 2010, 135: s29. DOI: 10.1016/j.clim.2010.03.091.Peer-Reviewed Original ResearchGraft-derived IL-6 Promotes Allogeneic T Cell Intimal Infiltration and Intimal Expansion in a Chimeric Mouse Model of Human Artery Rejection
Fogal B, Rao D, Yi T, Tellides G, Kulkarni S, Pober J. Graft-derived IL-6 Promotes Allogeneic T Cell Intimal Infiltration and Intimal Expansion in a Chimeric Mouse Model of Human Artery Rejection. Clinical Immunology 2010, 135: s42. DOI: 10.1016/j.clim.2010.03.127.Peer-Reviewed Original Research
2000
Interferon-γ elicits arteriosclerosis in the absence of leukocytes
Tellides G, Tereb D, Kirkiles-Smith N, Kim R, Wilson J, Schechner J, Lorber M, Pober J. Interferon-γ elicits arteriosclerosis in the absence of leukocytes. Nature 2000, 403: 207-211. PMID: 10646607, DOI: 10.1038/35003221.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArteriosclerosisCell DivisionCells, CulturedCoronary VesselsHistocompatibility AntigensHumansImage Processing, Computer-AssistedImmunohistochemistryInterferon-gammaLeukocytesMiceMice, SCIDMuscle, Smooth, VascularPlatelet-Derived Growth FactorReceptor, Platelet-Derived Growth Factor betaSwineTransplantation, HeterologousConceptsVascular smooth muscle cellsGraft arteriosclerosisIntimal expansionAbsence of leukocytesLesions of atherosclerosisSmooth muscle cellsAllogeneic transplantationArteriosclerotic changesAtheroma formationCytokine interferonExogenous IFNAntigen presentationT cellsImmunodeficient miceMononuclear leukocytesMouse modelArterial intimaIFNMuscle cellsArteriosclerosisLeukocytesHuman arteriesAtherosclerosisCellsTransplantation