2024
SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling
Xu Y, Zhang H, Chen Y, Pober J, Zhou M, Zhou J, Min W. SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling. Nature Communications 2024, 15: 6919. PMID: 39134547, PMCID: PMC11319592, DOI: 10.1038/s41467-024-51350-5.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSerum response factorCardiovascular diseaseVSMC synthetic phenotypeVascular remodelingNeointimal formationSENP1 deficiencySerum response factor activitySmooth muscle phenotypic switchingPhenotypic switchingPathogenesis of cardiovascular diseaseSmooth muscle cellsPost-translational SUMOylationTreatment of cardiovascular diseasesInhibitor AZD6244Phospho-ELK1Increased nuclear accumulationLysosomal localizationGene transcriptionNuclear accumulationMuscle cellsCoronary arteryCVD patientsVSMC phenotypic switchTherapeutic potentialEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Piotrowski-Daspit A, Bracaglia L, Eaton D, Richfield O, Binns T, Albert C, Gould J, Mortlock R, Egan M, Pober J, Saltzman W. Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys. Nature Communications 2024, 15: 4247. PMID: 38762483, PMCID: PMC11102454, DOI: 10.1038/s41467-024-48442-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrug Delivery SystemsFemaleHumansMacrophagesMiceMice, Inbred C57BLNanoparticlesPolymersTissue DistributionConceptsPoly(amine-co-esterPolymer nanoparticlesDelivery of nucleic acid therapeuticsCell-type tropismTissue tropismNucleic acid delivery vehiclesIn vivo deliveryIn vivo efficacyCirculation half-lifeNucleic acid therapeuticsVehicle characteristicsTunable propertiesBiodistribution assessmentPhysiological fatePolymer chemistrySurface propertiesPharmacokinetic modelTissue targetingNanoparticlesDistribution modifiersPolymeric nanoparticlesTropismPolymerDelivery vehiclesHalf-life
2023
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 signaling
2021
Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation
Lei I, Huang W, Ward PA, Pober JS, Tellides G, Ailawadi G, Pagani FD, Landstrom AP, Wang Z, Mortensen RM, Cascalho M, Platt J, Chen Y, Lam HYK, Tang PC. Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiological Reports 2021, 9: e15004. PMID: 34435466, PMCID: PMC8387788, DOI: 10.14814/phy2.15004.Peer-Reviewed Original ResearchConceptsRight ventricleCold ischemiaIL-10Inflammatory responseIL-6 protein levelsCold ischemic preservationEx vivo ischemiaLeft ventricle dysfunctionCold ischemic timeDonor heart preservationInflammatory cytokine expressionCell deathDifferential inflammatory responseTumor necrosis factorComparable inflammatory responsesHuman donor heartsCaspase-3 expressionIschemic preservationVentricle dysfunctionInflammasome expressionIschemic timeRNA sequencingContractile dysfunctionDonor heartsWarm perfusion
2015
Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli
Chang WG, Fornoni A, Tietjen G, Mendez JJ, Niklason LE, Saltzman WM, Pober JS. Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. Tissue Engineering Part A 2015, 21: 2673-2679. PMID: 26414101, PMCID: PMC4652181, DOI: 10.1089/ten.tea.2015.0060.Peer-Reviewed Original Research
2000
Selective Inhibition of NF-κB Activation by a Peptide That Blocks the Interaction of NEMO with the IκB Kinase Complex
May M, D'Acquisto F, Madge L, Glöckner J, Pober J, Ghosh S. Selective Inhibition of NF-κB Activation by a Peptide That Blocks the Interaction of NEMO with the IκB Kinase Complex. Science 2000, 289: 1550-1554. PMID: 10968790, DOI: 10.1126/science.289.5484.1550.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnti-Inflammatory Agents, Non-SteroidalCells, CulturedCOS CellsE-SelectinEndothelium, VascularGene Expression RegulationHeLa CellsHumansI-kappa B KinaseInflammationMiceMice, Inbred C57BLMolecular Sequence DataMutationNF-kappa BPeptidesPoint MutationProtein Serine-Threonine KinasesProtein Structure, TertiaryRecombinant Fusion ProteinsConceptsNF-kappaBBasal NF-kappaB activityExperimental mouse modelTranscription factor nuclear factorCytokine-induced NF-kappaB activationCell-permeable NBD peptideInhibitor of kappaBNF-κB activationNF-kappaB activityNF-kappaB activationAssociation of NEMOIKK complexAcute inflammationDevelopment of drugsProinflammatory activationInflammatory responseNBD peptideMouse modelProinflammatory stimuliIκB kinase (IKK) complexNuclear factorRegulatory protein NEMOInflammationSelective inhibitionExpression of genesHuman 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