2023
Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve
Ahmad A, Ghim M, Toczek J, Neishabouri A, Ojha D, Zhang Z, Gona K, Raza M, Jung J, Kukreja G, Zhang J, Guerrera N, Liu C, Sadeghi M. Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve. Journal Of Nuclear Medicine 2023, 64: 1487-1494. PMID: 37321825, PMCID: PMC10478817, DOI: 10.2967/jnumed.123.265516.Peer-Reviewed Original ResearchConceptsF-NaF PET/CTCalcific aortic valve diseaseBicuspid aortic valvePET/CTAortic valve calcificationAortic valve diseaseAortic valveAortic stenosisValve calcificationValvular calcificationValve diseaseF-NaFSubset of miceTricuspid aortic valveDevelopment of calcificationSignificant correlationUnderwent echocardiographyMedical therapyHigh prevalencePreclinical modelsMurine modelTherapeutic interventionsAge groupsAutoradiography dataMultimodality imaging
2018
Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation
Ye Y, Toczek J, Gona K, Kim HY, Han J, Razavian M, Golestani R, Zhang J, Wu TL, Ghosh M, Jung JJ, Sadeghi MM. Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation. Scientific Reports 2018, 8: 11647. PMID: 30076321, PMCID: PMC6076275, DOI: 10.1038/s41598-018-29941-2.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinasesMMP inhibitorsLung tissueTransgenic miceMMP activityHigh radiochemical purityHydroxamate MMP inhibitorsNumber of diseasesTissue remodelingSimilar inhibition potencyPotent inhibitionTherapySpecific bindingInhibitorsMolecular imagingImagingNovel arginineRadiochemical purityTissueHigh radiochemical yieldNew arginine
2017
VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylation
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 vesselsExpressionVangl2RemodelingCellsMorphogenesisEngineered Tissue–Stent Biocomposites as Tracheal Replacements
Zhao L, Sundaram S, Le AV, Huang AH, Zhang J, Hatachi G, Beloiartsev A, Caty MG, Yi T, Leiby K, Gard A, Kural MH, Gui L, Rocco KA, Sivarapatna A, Calle E, Greaney A, Urbani L, Maghsoudlou P, Burns A, DeCoppi P, Niklason LE. Engineered Tissue–Stent Biocomposites as Tracheal Replacements. Tissue Engineering Part A 2016, 22: 1086-1097. PMID: 27520928, PMCID: PMC5312617, DOI: 10.1089/ten.tea.2016.0132.Peer-Reviewed Original ResearchIntegrin 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
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J, Zhang J, Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 2015, 133: 409-421. PMID: 26659946, PMCID: PMC4729599, DOI: 10.1161/circulationaha.115.017537.Peer-Reviewed Original ResearchConceptsFront-rear polaritySprouting angiogenesisSignal integration mechanismImportant drug targetsNck adaptorsCytoskeletal dynamicsEndothelial cell migrationEmbryonic developmentAngiogenesis defectsPAK2 activationVessel sproutsNumber of diseasesBlood vessel growthDrug targetsCell migrationPostnatal retinaAngiogenic growthNckNck1AdaptorVessel growthKey processesEndothelial cellsPathological ocular neovascularizationInhibits neovascularizationImpaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease
Srivastava R, Zhang J, Go GW, Narayanan A, Nottoli TP, Mani A. Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease. Cell Reports 2015, 13: 746-759. PMID: 26489464, PMCID: PMC4626307, DOI: 10.1016/j.celrep.2015.09.028.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseLRP6 activityArtery diseaseObstructive coronary artery diseaseHigh-fat dietVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationAtherosclerotic burdenMedial hyperplasiaCarotid injuryArterial diseaseVascular obstructionNeointima formationTherapeutic targetWnt3a administrationIntact WntVSMC differentiationKnockout backgroundDiseaseMiceVessel wallNon-canonical WntCoreceptor LRP6Cell plasticityMultimodality and Molecular Imaging of Matrix Metalloproteinase Activation in Calcific Aortic Valve Disease
Jung JJ, Razavian M, Challa AA, Nie L, Golestani R, Zhang J, Ye Y, Russell KS, Robinson SP, Heistad DD, Sadeghi MM. Multimodality and Molecular Imaging of Matrix Metalloproteinase Activation in Calcific Aortic Valve Disease. Journal Of Nuclear Medicine 2015, 56: 933-938. PMID: 25908827, PMCID: PMC4454445, DOI: 10.2967/jnumed.114.152355.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic ValveAortic Valve StenosisApolipoproteins EBicuspid Aortic Valve DiseaseCalcinosisDiet, High-FatEchocardiographyHeart Defects, CongenitalHeart Valve DiseasesHumansMatrix MetalloproteinasesMiceMice, TransgenicMolecular ImagingMultimodal ImagingTechnetiumTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedConceptsCalcific aortic valve diseaseAortic valve diseaseMatrix metalloproteinasesWestern dietValve diseaseValvular inflammationMMP activityDevelopment of CAVDMedical therapeutic interventionsAortic valve areaSPECT/CT imagesWild-type miceMatrix metalloproteinase activationAortic stenosisMolecular imagingValvular calcificationControl miceCD68 expressionValve areaWD miceDeficient miceCommon causeApolipoprotein ECD68 stainingMurine model
2014
Chemokine-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 VEGF
2012
Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis
Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM. Molecular Imaging of Vascular Endothelial Growth Factor Receptors in Graft Arteriosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2012, 32: 1849-1855. PMID: 22723442, PMCID: PMC3401339, DOI: 10.1161/atvbaha.112.252510.Peer-Reviewed Original ResearchConceptsGraft arteriosclerosisArtery graftVascular remodelingAllogeneic human peripheral blood mononuclear cellsHuman coronary artery segmentsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsSevere combined immunodeficiency miceVEGF receptorsVascular endothelial growth factor receptorLate organ failureHuman coronary artery graftsSolid organ transplantationCoronary artery graftsEndothelial growth factor receptorBlood mononuclear cellsCoronary artery segmentsCombined immunodeficiency miceReceptor 2 expressionVEGF receptor-2 expressionMolecular imagingSignificant neointima formationVascular endothelial growth factor signalingVEGF receptor 1Growth factor receptor
2010
VEGF Blockade Inhibits Lymphocyte Recruitment and Ameliorates Immune-Mediated Vascular Remodeling
Zhang J, Silva T, Yarovinsky T, Manes TD, Tavakoli S, Nie L, Tellides G, Pober JS, Bender JR, Sadeghi MM. VEGF Blockade Inhibits Lymphocyte Recruitment and Ameliorates Immune-Mediated Vascular Remodeling. Circulation Research 2010, 107: 408-417. PMID: 20538685, PMCID: PMC2929975, DOI: 10.1161/circresaha.109.210963.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedArteriesBevacizumabCD3 ComplexCoronary VesselsHumansJurkat CellsLymphocytesMiceMice, SCIDReceptors, Vascular Endothelial Growth FactorT-LymphocytesTransplantation, HeterologousVascular Endothelial Growth Factor AConceptsVascular endothelial growth factorRole of VEGFAdhesion molecule-1T cellsVascular remodelingHuman T cellsMolecule-1Recombinant intercellular adhesion molecule-1Human arteriesVascular cell adhesion molecule-1Intercellular adhesion molecule-1Cell adhesion molecule-1Inhibition of VEGFT cell accumulationPeripheral blood mononuclearEffects of VEGFSubpopulation of CD3Novel therapeutic approachesEndothelial growth factorT cell activationT cell linesVEGFR-1 mRNAT cell captureLymphocyte recruitmentBlood mononuclear
2005
αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study
Zhang J, Krassilnikova S, Gharaei AA, Fassaei HR, Esmailzadeh L, Asadi A, Edwards DS, Harris TD, Azure M, Tellides G, Sinusas AJ, Zaret BL, Bender JR, Sadeghi MM. αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study. The FASEB Journal 2005, 19: 1857-1859. PMID: 16150802, DOI: 10.1096/fj.05-4130fje.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAutoradiographyCarotid Artery DiseasesCell MovementCell ProliferationCell TransplantationCells, CulturedChimeraCoronary VesselsDensitometryEndothelium, VascularHeart TransplantationHeterocyclic Compounds, 1-RingHumansImmunohistochemistryIntegrin alphaVbeta3Ki-67 AntigenLeukocytes, MononuclearMiceMice, SCIDMicroscopy, FluorescenceOrganometallic CompoundsRecombinant Fusion ProteinsTime FactorsTissue TransplantationUp-RegulationVascular DiseasesConceptsPeripheral blood mononuclear cellsGraft arteriopathyHuman coronary arteriesCoronary arteryAllogeneic human peripheral blood mononuclear cellsHuman/mouse chimeric modelAlphavbeta3 expressionHuman peripheral blood mononuclear cellsProliferative processesSevere combined immunodeficiency miceLate graft failureBlood mononuclear cellsCombined immunodeficiency miceAlphavbeta3 integrinSpecificity of uptakeCardiac transplantationConcentric narrowingGraft failureMononuclear cellsImmunodeficiency miceVascular remodelingNeointima formationNative aortaChimeric modelAutoradiographic study