2023
Homeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity
Salarian M, Ghim M, Toczek J, Han J, Weiss D, Spronck B, Ramachandra A, Jung J, Kukreja G, Zhang J, Lakheram D, Kim S, Humphrey J, Sadeghi M. Homeostatic, Non-Canonical Role of Macrophage Elastase in Vascular Integrity. Circulation Research 2023, 132: 432-448. PMID: 36691905, PMCID: PMC9930896, DOI: 10.1161/circresaha.122.322096.Peer-Reviewed Original ResearchConceptsMMP-12 deficiencyAdverse aortic remodelingAbdominal aortic aneurysmAng IIAortic remodelingAortic aneurysmMMP-12Complement component 3 levelsNeutrophil extracellular traps markersAbdominal aortic aneurysm ruptureAortic aneurysm ruptureElastic lamina degradationPlasma complement componentsAortic ruptureC3 levelsComplement depositionPlasma C5aMore neutrophilsVascular remodelingAneurysm ruptureNeutrophil elastaseAortic integrityMatrix metalloproteinaseComplement inhibitorsNETosis pathway
2021
Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm
Toczek J, Boodagh P, Sanzida N, Ghim M, Salarian M, Gona K, Kukreja G, Rajendran S, Wei L, Han J, Zhang J, Jung JJ, Graham M, Liu X, Sadeghi MM. Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm. Theranostics 2021, 11: 5876-5888. PMID: 33897887, PMCID: PMC8058712, DOI: 10.7150/thno.55106.Peer-Reviewed Original ResearchConceptsAbdominal aortic aneurysmExiTron nano 12000AAA outcomePhagocytic activityII infusionAng IIAortic aneurysmAortic wall enhancementAng II infusionCT enhancementAngiotensin II infusionRole of inflammationFeasibility of CTMacrophage phagocytic activityNon-invasive toolAAA inductionCD68 expressionModulatory interventionsMacrophage cell lineInflammatory signalsPatient managementVascular pathologyOutcome studiesAdventitial macrophagesComputed tomography
2018
Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
2017
PKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury
Yuan Q, Ren C, Xu W, Petri B, Zhang J, Zhang Y, Kubes P, Wu D, Tang W. PKN1 Directs Polarized RAB21 Vesicle Trafficking via RPH3A and Is Important for Neutrophil Adhesion and Ischemia-Reperfusion Injury. Cell Reports 2017, 19: 2586-2597. PMID: 28636945, PMCID: PMC5548392, DOI: 10.1016/j.celrep.2017.05.080.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell AdhesionCell PolarityFemaleKidneyMaleMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeutrophilsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Kinase CProtein Processing, Post-TranslationalProtein TransportRab GTP-Binding ProteinsReperfusion InjuryTransendothelial and Transepithelial MigrationTransport VesiclesVesicular Transport ProteinsConceptsTissue injuryNeutrophil adhesionRenal ischemia-reperfusion modelEndothelial cellsDecrease tissue injuryMyeloid-specific lossIschemia-reperfusion injuryIschemia-reperfusion modelInnate immune responseNeutrophil integrin activationInflammatory modelInflammatory responseImmune responseTherapeutic interventionsInjuryNeutrophilsRPH3AIntegrin activationCellsFGF-dependent metabolic control of vascular development
Yu P, Wilhelm K, Dubrac A, Tung JK, Alves TC, Fang JS, Xie Y, Zhu J, Chen Z, De Smet F, Zhang J, Jin SW, Sun L, Sun H, Kibbey RG, Hirschi KK, Hay N, Carmeliet P, Chittenden TW, Eichmann A, Potente M, Simons M. FGF-dependent metabolic control of vascular development. Nature 2017, 545: 224-228. PMID: 28467822, PMCID: PMC5427179, DOI: 10.1038/nature22322.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCell ProliferationEndothelial CellsFemaleFibroblast Growth FactorsGlycolysisHexokinaseLymphangiogenesisLymphatic VesselsMiceMice, Inbred C57BLNeovascularization, PhysiologicProto-Oncogene Proteins c-mycReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 3Signal Transduction
2016
Optical imaging of MMP-12 active form in inflammation and aneurysm
Razavian M, Bordenave T, Georgiadis D, Beau F, Zhang J, Golestani R, Toczek J, Jung JJ, Ye Y, Kim HY, Han J, Dive V, Devel L, Sadeghi MM. Optical imaging of MMP-12 active form in inflammation and aneurysm. Scientific Reports 2016, 6: 38345. PMID: 27917892, PMCID: PMC5137160, DOI: 10.1038/srep38345.Peer-Reviewed Original ResearchMeSH KeywordsAneurysmAnimalsAntigens, DifferentiationCarotid ArteriesDisease Models, AnimalFluorescent DyesGene ExpressionHumansInflammationMacrophagesMatrix Metalloproteinase 12Matrix Metalloproteinase InhibitorsMiceMice, Inbred C57BLOptical ImagingPeptidesProtein BindingQuaternary Ammonium CompoundsSulfonic AcidsConceptsProbe 3Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development
Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development 2016, 143: 4441-4451. PMID: 27789626, PMCID: PMC5201046, DOI: 10.1242/dev.140129.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsPlanar cell polarity protein Vangl2Lymphatic vessel remodelingMouse embryonic developmentHuman lymphatic endothelial cellsVangl2 overexpressionVangl2 expressionEmbryonic developmentValve morphogenesisEndothelial cellsVasculature developmentSyndecan-4Lymphatic vasculatureFluid shear stressSDC4Double knockout miceMice resultsHigh expressionVessel remodelingLymphatic vesselsExpressionVangl2RemodelingCellsMorphogenesisThe neuropilin-like protein ESDN regulates insulin signaling and sensitivity
Li X, Jung JJ, Nie L, Razavian M, Zhang J, Samuel V, Sadeghi MM. The neuropilin-like protein ESDN regulates insulin signaling and sensitivity. AJP Heart And Circulatory Physiology 2016, 310: h1184-h1193. PMID: 26921437, PMCID: PMC4867389, DOI: 10.1152/ajpheart.00782.2015.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDAorta, ThoracicCell MovementCell ProliferationCells, CulturedDose-Response Relationship, DrugEnzyme ActivationFemaleGenotypeGRB10 Adaptor ProteinInsulinInsulin ResistanceMaleMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropilinsPhenotypePhosphorylationProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionTime FactorsUbiquitinationConceptsSignal transductionNovel regulatorSmooth muscle cell-derived neuropilin-like proteinInsulin receptorInsulin receptor signal transductionMitogen-activated protein kinase activationSrc homology 2Novel regulatory mechanismReceptor signal transductionProtein kinase BInsulin signal transductionProtein kinase activationInsulin receptor phosphorylationPleckstrin homologyHomology 2Adaptor proteinTransmembrane proteinGrowth factor receptorKinase activationVascular smooth muscle cell proliferationRegulatory mechanismsKinase BInsulin signalingReceptor phosphorylationNovel therapeutic avenuesIntegrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis
Misra A, Sheikh AQ, Kumar A, Luo J, Zhang J, Hinton RB, Smoot L, Kaplan P, Urban Z, Qyang Y, Tellides G, Greif DM. Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. Journal Of Experimental Medicine 2016, 213: 451-463. PMID: 26858344, PMCID: PMC4813675, DOI: 10.1084/jem.20150688.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMutant miceTherapeutic strategiesAortic stenosis patientsAortic smooth muscle cellsSupravalvular aortic stenosisAttractive therapeutic strategyIntegrin β3 levelsAortic pathologyAortic stenosisStenosis patientsArterial diseaseLumen lossPathological featuresArterial mediaLarge arteriesAortic mediaElastin deficiencyPharmacological inhibitionMuscle cellsStenosisMicePathological stenosisExplant culturesSVAS patients
2015
Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients
Zhou J, Qin L, Yi T, Ali R, Li Q, Jiao Y, Li G, Tobiasova Z, Huang Y, Zhang J, Yun JJ, Sadeghi MM, Giordano FJ, Pober JS, Tellides G. Interferon-&ggr;–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients. Circulation Research 2015, 117: 943-955. PMID: 26399469, PMCID: PMC4636943, DOI: 10.1161/circresaha.115.306932.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisCardiomyopathiesCardiovascular DiseasesDisease Models, AnimalFemaleGraft RejectionHeart TransplantationHemodynamicsHistocompatibility Antigens Class IIHyperlipidemiasInflammation MediatorsInterferon-gammaLymphocyte ActivationMaleMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutSignal TransductionTh1 CellsVentricular Dysfunction, LeftVentricular Function, LeftConceptsOrgan transplant recipientsCardiovascular diseaseTransplant recipientsEarly-onset cardiovascular diseaseEnd-stage organ failureNative coronary arteriesTh1-type cytokinesT helper cellsHost diseaseAlloimmune responseGraft rejectionAortic stiffeningOrgan failureVentricular dilatationAllogeneic graftsCardiovascular dysfunctionCoronary arteryAortic complianceRisk factorsEffective therapyCardiac contractilityMurine modelAnimal modelsSerological neutralizationImmune system
2014
Imaging Vessel Wall Biology to Predict Outcome in Abdominal Aortic Aneurysm
Golestani R, Razavian M, Nie L, Zhang J, Jung JJ, Ye Y, de Roo M, Hilgerink K, Liu C, Robinson SP, Sadeghi MM. Imaging Vessel Wall Biology to Predict Outcome in Abdominal Aortic Aneurysm. Circulation Cardiovascular Imaging 2014, 8: &na;. PMID: 25550400, PMCID: PMC4284949, DOI: 10.1161/circimaging.114.002471.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticAorta, AbdominalAortic Aneurysm, AbdominalAortic RuptureAortographyBiomarkersDisease Models, AnimalDisease ProgressionEnzyme ActivationFeasibility StudiesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, TransgenicMolecular ImagingMultimodal ImagingPredictive Value of TestsRadiopharmaceuticalsRisk AssessmentRisk FactorsTime FactorsTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsMicro-single photon emissionAngiotensin IIMatrix metalloproteinasesAortic diameterSuprarenal aortaCD68 expressionMMP activityPotential of MMPSaline-infused miceVessel wall inflammationAbdominal aortic aneurysmPrediction of outcomePhoton emissionRupture riskMurine AAAsAortic expansionRisk stratificationWall inflammationAortic aneurysmSpontaneous ruptureSmall aneurysmsMouse modelControl animalsTracer uptakeAbdominal aortic aneurysm (AAA) rupture riskELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis
Chang SH, Elemento O, Zhang J, Zhuang ZW, Simons M, Hla T. ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 18309-18314. PMID: 25422430, PMCID: PMC4280608, DOI: 10.1073/pnas.1412172111.Peer-Reviewed Original ResearchConceptsProcessing bodiesAlternative splicingEmbryonic lethal abnormal visionRNA processing bodiesNovel posttranscriptional mechanismRNA regulationMRNA turnoverCellular phenotypesPosttranscriptional mechanismsShort isoformTransporter proteinsCellular behaviorPostnatal angiogenesisAngiogenic mRNAsSplicingSprouting behaviorVascular endothelial cellsPathological angiogenesisFactor 1ELAVL1ProteinReduced revascularizationEndothelial cellsExon 11Tumor angiogenesisChemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis
Morrison AR, Yarovinsky TO, Young BD, Moraes F, Ross TD, Ceneri N, Zhang J, Zhuang ZW, Sinusas AJ, Pardi R, Schwartz MA, Simons M, Bender JR. Chemokine-coupled β2 integrin–induced macrophage Rac2–Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. Journal Of Experimental Medicine 2014, 211: 1957-1968. PMID: 25180062, PMCID: PMC4172219, DOI: 10.1084/jem.20132130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriesCD18 AntigensDNA PrimersFlow CytometryHumansMiceMice, Inbred C57BLMonocytesNeovascularization, PhysiologicNonmuscle Myosin Type IIARac GTP-Binding ProteinsReal-Time Polymerase Chain ReactionReceptors, CCR2RNA StabilityVascular Endothelial Growth Factor AX-Ray MicrotomographyConceptsMyosin IIASignal transduction eventsHuR translocationRapid nuclearTransduction eventsProteomic analysisProtein HuR.Induction of arteriogenesisMRNA stabilityMRNA stabilizationNovel roleCytosolic translocationMyosin-9ICAM-1 adhesionReceptor engagementDevelopmental vasculogenesisCellular effectorsMolecular triggersTranslocationHeavy chainGrowth factorMyeloid cellsVascular endothelial growth factorKey molecular triggerCCL2 stimulation
2013
Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM. Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. Journal Of Clinical Investigation 2013, 123: 5082-5097. PMID: 24177422, PMCID: PMC3859420, DOI: 10.1172/jci67752.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBlood VesselsCadherinsCells, CulturedEar, ExternalEndothelium, VascularHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNeuropilinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 2Retinal VesselsRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ZebrafishZebrafish ProteinsConceptsSmooth muscle cell-derived neuropilin-like proteinAberrant blood vessel formationNormal vascular developmentProtein tyrosineTC-PTPTransmembrane proteinTherapeutic targetBlood vessel formationVEGF responseNegative regulatorDevelopmental angiogenesisVEGFR-2Vascular developmentAttractive therapeutic targetESDNAngiogenesis regulationVE-cadherinVessel formationEC proliferationComplex formationRegulatorProteinNeuropilin expressionVEGF receptorsEndothelial VEGFA Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils
Zhang Y, Tang W, Zhang H, Niu X, Xu Y, Zhang J, Gao K, Pan W, Boggon TJ, Toomre D, Min W, Wu D. A Network of Interactions Enables CCM3 and STK24 to Coordinate UNC13D-Driven Vesicle Exocytosis in Neutrophils. Developmental Cell 2013, 27: 215-226. PMID: 24176643, PMCID: PMC3834565, DOI: 10.1016/j.devcel.2013.09.021.Peer-Reviewed Original ResearchConceptsNeutrophil degranulationAcute innate immune responseIschemia-reperfusion injuryInnate immune responseProtection of kidneyNeutrophil functionImmune responseInhibition of exocytosisTissue damageGranule poolGranule contentsDegranulationImportant regulatorImportant roleVesicle exocytosisExocytosisSTK24InjuryNeutrophilsKidneyUNC13DEndothelial Cell–Dependent Regulation of Arteriogenesis
Moraes F, Paye J, Mac Gabhann F, Zhuang ZW, Zhang J, Lanahan AA, Simons M. Endothelial Cell–Dependent Regulation of Arteriogenesis. Circulation Research 2013, 113: 1076-1086. PMID: 23897694, PMCID: PMC3865810, DOI: 10.1161/circresaha.113.301340.Peer-Reviewed Original ResearchConceptsAdult arteriogenesisCell-autonomous fashionGrowth factor signalingMouse linesCell-autonomous effectsKnockin mouse lineMorphogenetic defectsArterial morphogenesisCell type-specific deletionFactor signalingCell typesCre-driver mouse linesSynectinAttractive therapeutic strategyOcclusive atherosclerotic diseaseMuscle cellsEndothelial cellsRegulationArterial conduitsAtherosclerotic diseaseTherapeutic strategiesAdult miceClinical importanceArteriogenesisCells