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 transitionStiffening 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 remodelingDe 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 integrityIntimomedial 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
Multiscale insights into postnatal aortic development
Rego B, Murtada S, Li G, Tellides G, Humphrey J. Multiscale insights into postnatal aortic development. Biomechanics And Modeling In Mechanobiology 2023, 23: 687-701. PMID: 38151614, PMCID: PMC11419831, DOI: 10.1007/s10237-023-01800-8.Peer-Reviewed Original ResearchAuthor Correction: 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. Author Correction: A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature Communications 2023, 14: 8404. PMID: 38110370, PMCID: PMC10728129, DOI: 10.1038/s41467-023-44225-8.Peer-Reviewed Original ResearchHedgehog 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 treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4Author Correction: 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. Author Correction: A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells. Nature Communications 2023, 14: 3336. PMID: 37286577, PMCID: PMC10247709, DOI: 10.1038/s41467-023-39154-5.Peer-Reviewed Original ResearchA 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 accumulationMiceBiomechanical 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 calcificationThe Extracellular Matrix of the Human Proximal Pulmonary Artery Regulates Gene Expression of Resident Cells Responsible for Remodeling During Aging
Yuan Y, Khoury J, Ramachandra A, Singh I, Tellides G, Humphrey J, Kaminski N, Manning E. The Extracellular Matrix of the Human Proximal Pulmonary Artery Regulates Gene Expression of Resident Cells Responsible for Remodeling During Aging. 2023, a2680-a2680. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a2680.Peer-Reviewed Original ResearchAge-related Changes in Structure, Function, and Transcriptomics of the Human Proximal Pulmonary Artery
Manning E, Ramachandra A, Cavinato C, Schupp J, Justet A, Lee P, Heerdt P, Singh I, Murphy T, Gill T, Tellides G, Kaminski N, Humphrey J. Age-related Changes in Structure, Function, and Transcriptomics of the Human Proximal Pulmonary Artery. 2023, a4656-a4656. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a4656.Peer-Reviewed Original ResearchPulmonary Hypertension-related Changes in Structure and Function of the Human Proximal Pulmonary Artery
Manning E, Ramachandra A, Cavinato C, Lee P, Heerdt P, Singh I, Tellides G, Kaminski N, Humphrey J. Pulmonary Hypertension-related Changes in Structure and Function of the Human Proximal Pulmonary Artery. 2023, a6133-a6133. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a6133.Peer-Reviewed Original ResearchFN (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