2024
Stiffening of the human proximal pulmonary artery with increasing age
Manning E, Mishall P, Ramachandra A, Hassab A, Lamy J, Peters D, Murphy T, Heerdt P, Singh I, Downie S, Choudhary G, Tellides G, Humphrey J. Stiffening of the human proximal pulmonary artery with increasing age. Physiological Reports 2024, 12: e16090. PMID: 38884325, PMCID: PMC11181131, DOI: 10.14814/phy2.16090.Peer-Reviewed Original ResearchConceptsProximal pulmonary arteriesPulmonary arteryAge-related stiffeningRight ventricular ejection fractionVentricular ejection fractionMean wall thicknessEjection fractionNo significant differenceSystemic circulationLuminal caliberDiffusing capacityArterial stiffeningIncreasing ageSignificant differenceDistensionArteryWall thicknessAdverse effectsWall strainVessel diameterCyclic biaxial strainOrgan donorsAgeMicrostructural remodelingIntimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis
Hassab A, Hur D, Vallabhajosyula P, Tellides G, Assi R. Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis. JCI Insight 2024, 9: e172437. PMID: 38592807, PMCID: PMC11141924, DOI: 10.1172/jci.insight.172437.Peer-Reviewed Original ResearchConceptsDepartment of SurgerySmooth muscle cellsCellular response to injuryResponse to injuryImmunofluorescence confocal microscopyVessel wall repairPrimary lesionAscending aortaConduit functionAneurysmal diseaseDense fibrosisRadiological signsMural hematomaTear progressionMuscle cellsNon-hemorrhagicErythrocyte extravasationWall repairAortaTear completionInduce atherosclerosisHealed lesionsScattered leukocytesMinimal injuryConclusionThese findings
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 subsetsRecruited macrophages elicit atrial fibrillation
Hulsmans M, Schloss M, Lee I, Bapat A, Iwamoto Y, Vinegoni C, Paccalet A, Yamazoe M, Grune J, Pabel S, Momin N, Seung H, Kumowski N, Pulous F, Keller D, Bening C, Green U, Lennerz J, Mitchell R, Lewis A, Casadei B, Iborra-Egea O, Bayes-Genis A, Sossalla S, Ong C, Pierson R, Aster J, Rohde D, Wojtkiewicz G, Weissleder R, Swirski F, Tellides G, Tolis G, Melnitchouk S, Milan D, Ellinor P, Naxerova K, Nahrendorf M. Recruited macrophages elicit atrial fibrillation. Science 2023, 381: 231-239. PMID: 37440641, PMCID: PMC10448807, DOI: 10.1126/science.abq3061.Peer-Reviewed Original ResearchConceptsAtrial fibrillationStromal cellsMitral valve regurgitationHeart failureValve regurgitationInflammatory monocytesMacrophage expansionMonocyte migrationMouse atriaFibrillationHuman atriumAtriumCell-cell interaction analysisSingle-cell transcriptomesMiceCell compositionHypertensionTranscriptome changesImmunotherapySPP1CellsRegurgitationObesityPatientsArrhythmiasAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4A 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 modelRNF34CellsBiomechanical and transcriptional evidence that smooth muscle cell death drives an osteochondrogenic phenotype and severe proximal vascular disease in progeria
Murtada S, Kawamura Y, Cavinato C, Wang M, Ramachandra A, Spronck B, Li D, Tellides G, Humphrey J. Biomechanical and transcriptional evidence that smooth muscle cell death drives an osteochondrogenic phenotype and severe proximal vascular disease in progeria. Biomechanics And Modeling In Mechanobiology 2023, 22: 1333-1347. PMID: 37149823, PMCID: PMC10544720, DOI: 10.1007/s10237-023-01722-5.Peer-Reviewed Original ResearchConceptsPulse wave velocitySmooth muscle cell deathMuscle cell deathDisease processOsteochondrogenic phenotypeAdverse extracellular matrix remodelingImportant cardiovascular implicationsProgressive aortic diseaseProximal elastic arteriesVentricular diastolic dysfunctionProgressive disease processSmooth muscle cellsCell deathCardiovascular sequelaeDiastolic dysfunctionCardiovascular implicationsExtracellular matrix remodelingAortic diseasePrimary diagnosisVascular diseaseAccumulation of proteoglycansMuscular arteriesAortic structureAortic wallLate calcificationHedgehog-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 signalingPositron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm
Toczek J, Gona K, Liu Y, Ahmad A, Ghim M, Ojha D, Kukreja G, Salarian M, Luehmann H, Heo G, Guzman R, Chaar C, Tellides G, Hassab A, Ye Y, Shoghi K, Zayed M, Gropler R, Sadeghi M. Positron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm. Circulation Cardiovascular Imaging 2023, 16: e014615. PMID: 36649454, PMCID: PMC9858355, DOI: 10.1161/circimaging.122.014615.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmHuman aortic tissueMMP activityAortic tissueAortic aneurysmMMP inhibitorsMurine modelMatrix metalloproteinasesPositron emission tomography/Toxicology studiesAortic MMP activityPositron emission tomography radioligandAngiotensin II infusionEmission tomography/Murine abdominal aortic aneurysmsBroad-spectrum MMP inhibitorMatrix metalloproteinase activityPositron emission tomography (PET) tracerPositron emission tomography (PET) imagingEmission Tomography ImagingPositron emission tomographyEmission tomography tracerII infusionRisk stratificationTomography/
2022
Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling
Canfrán-Duque A, Rotllan N, Zhang X, Andrés-Blasco I, Thompson B, Sun J, Price N, Fernández-Fuertes M, Fowler J, Gómez-Coronado D, Sessa W, Giannarelli C, Schneider R, Tellides G, McDonald J, Fernández-Hernando C, Suárez Y. Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling. Circulation 2022, 147: 388-408. PMID: 36416142, PMCID: PMC9892282, DOI: 10.1161/circulationaha.122.059062.Peer-Reviewed Original ResearchConceptsLipid-loaded macrophagesLineage-tracing mouse modelsSREBP transcriptional activityCholesterol biosynthetic intermediatesWestern diet feedingAccessible cholesterolDifferent macrophage populationsTranscriptomic analysisKey immune regulatorsPlasma membraneAtherosclerosis progressionImmune activationTranscriptional activityGene expressionDiet feedingInflammatory responseMouse bone marrowLiver X receptorBiosynthetic intermediatesSterol metabolismApoptosis susceptibilityToll-like receptor 4Proinflammatory gene expressionHuman coronary atherosclerotic lesionsMouse atherosclerotic plaques
2021
Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis
Zhang X, McDonald JG, Aryal B, Canfrán-Duque A, Goldberg EL, Araldi E, Ding W, Fan Y, Thompson BM, Singh AK, Li Q, Tellides G, Ordovás-Montanes J, García Milian R, Dixit VD, Ikonen E, Suárez Y, Fernández-Hernando C. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2107682118. PMID: 34782454, PMCID: PMC8617522, DOI: 10.1073/pnas.2107682118.Peer-Reviewed Original ResearchConceptsCholesterol biosynthetic intermediatesBiosynthetic intermediatesDependent inflammasome activationSingle-cell transcriptomicsMitochondrial reactive oxygen species productionFoam cell formationMacrophage foam cellsReactive oxygen species productionHuman coronary artery lesionsConversion of desmosterolTranscriptomic analysisMacrophage cholesterol metabolismPhysiological contextOxygen species productionLiver X receptor ligandsApoptosis-associated speck-like proteinRetinoid X receptor activationX receptor ligandsInflammasome activationAtherosclerotic plaquesSpeck-like proteinCholesterol homeostasisMacrophage inflammasome activationKey moleculesCell formationAdventitial 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
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
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
2016
Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice
Qin L, Li G, Kirkiles‐Smith N, Clark P, Fang C, Wang Y, Yu Z, Devore D, Tellides G, Pober J, Jane‐Wit D. Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice. American Journal Of Transplantation 2016, 16: 2865-2876. PMID: 27104811, PMCID: PMC5075274, DOI: 10.1111/ajt.13834.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryAllograft vasculopathyEndothelial cell activationReperfusion injuryCell activationComplement C5 inhibitionNuclear factor kappa BSolid organ transplantsT cell infiltrationTerminal complement activationVCAM-1 expressionComplement C5 activationFactor kappa BNeutrophil infiltrationHumanized miceDiffuse stenosisIntraluminal thrombosisArterial graftsC5 inhibitionCell infiltrationHumanized modelNeointimal hyperplasiaOrgan transplantsAlloantibodiesNF-kB
2001
Single-clamp technique does not protect against cerebrovascular accident in coronary artery bypass grafting⋆
Kim R, Mariconda D, Tellides G, Kopf G, Dewar M, Lin Z, Elefteriades J. Single-clamp technique does not protect against cerebrovascular accident in coronary artery bypass grafting⋆. European Journal Of Cardio-Thoracic Surgery 2001, 20: 127-132. PMID: 11423285, DOI: 10.1016/s1010-7940(01)00765-5.Peer-Reviewed Original ResearchConceptsSingle-clamp techniqueCoronary artery bypassPostoperative strokeArtery bypassStroke preventionCerebrovascular accidentSide-biting aortic clampAdverse myocardial effectsCross-clamp timePostoperative adverse eventsPerioperative myocardial infarctionCoronary bypass operationsLogistic regression analysisEmbolic consequencesHospital mortalityAdverse eventsAortic clampMyocardial effectsBypass operationMyocardial infarctionMyocardial protectionClinical practiceClamp techniqueSecond surgeonStrokeHUMAN 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
Effect of left ventricular volume on results of coronary artery bypass grafting
Kim R, Ugurlu B, Tereb D, Wackers F, Tellides G, Elefteriades J. Effect of left ventricular volume on results of coronary artery bypass grafting. The American Journal Of Cardiology 2000, 86: 1261-1264. PMID: 11090805, DOI: 10.1016/s0002-9149(00)01216-9.Peer-Reviewed Original ResearchConceptsCoronary artery bypassArtery bypassSignificant left ventricular dilationLeft ventricular dilationLV chamber sizeLV ejection fractionMedium-term survivalSurgical revascularizationAngina symptomsEjection fractionIschemic cardiomyopathyLV dilationVentricular dilationVentricular sizeVentricular volumePatientsSignificant reductionBypassChamber sizeDilationRevascularizationCardiomyopathySymptomsIn vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse
Schechner J, Nath A, Zheng L, Kluger M, Hughes C, Sierra-Honigmann M, Lorber M, Tellides G, Kashgarian M, Bothwell A, Pober J. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9191-9196. PMID: 10890921, PMCID: PMC16844, DOI: 10.1073/pnas.150242297.Peer-Reviewed Original ResearchHuman 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