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
2018
Endothelial Cell Autonomous Role of Akt1
Lee MY, Gamez-Mendez A, Zhang J, Zhuang Z, Vinyard DJ, Kraehling J, Velazquez H, Brudvig GW, Kyriakides TR, Simons M, Sessa WC. Endothelial Cell Autonomous Role of Akt1. Arteriosclerosis Thrombosis And Vascular Biology 2018, 38: 870-879. PMID: 29449333, PMCID: PMC6503971, DOI: 10.1161/atvbaha.118.310748.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicBlood Flow VelocityBlood PressureDisease Models, AnimalEndothelial CellsHindlimbIschemiaMaleMice, KnockoutMuscle, SkeletalNeovascularization, PhysiologicNitric OxideNitric Oxide Synthase Type IIIPhosphorylationProto-Oncogene Proteins c-aktRegional Blood FlowSignal TransductionVasoconstriction
2016
The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization
Zhang F, Prahst C, Mathivet T, Pibouin-Fragner L, Zhang J, Genet G, Tong R, Dubrac A, Eichmann A. The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization. Nature Communications 2016, 7: 13517. PMID: 27882935, PMCID: PMC5123080, DOI: 10.1038/ncomms13517.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCapillary PermeabilityDiabetic RetinopathyIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutNeovascularization, PathologicNerve Tissue ProteinsNetrin ReceptorsOxygen Inhalation TherapyPhosphorylationReceptors, Cell SurfaceReceptors, ImmunologicRetinal DiseasesRetinopathy of PrematuritySignal TransductionVascular Endothelial Growth Factor Receptor-2Wound HealingConceptsCytoplasmic domainOxygen-induced retinopathyVascular permeabilityRetinopathy of prematurityTransmembrane receptorsWound healingDiabetic wound healingCutaneous wound healingDiabetic patientsUNC5B receptorRobo4Transgenic miceTissue revascularizationRevascularizationVessel permeabilityRetinopathyMiceHealingNeovascularizationReceptorsDomainPhosphorylationDeletionPrematurityPathwaySyndecan 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 avenuesmiR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart
Li N, Hwangbo C, Jaba IM, Zhang J, Papangeli I, Han J, Mikush N, Larrivée B, Eichmann A, Chun HJ, Young LH, Tirziu D. miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart. Scientific Reports 2016, 6: 21228. PMID: 26888314, PMCID: PMC4758045, DOI: 10.1038/srep21228.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyEndotheliumMechanistic Target of Rapamycin Complex 1Membrane ProteinsMiceMice, KnockoutMicroRNAsMultiprotein ComplexesMyocytes, CardiacNeovascularization, PathologicNitric OxideNitric Oxide Synthase Type IIIProteinsProto-Oncogene Proteins c-aktRGS ProteinsTOR Serine-Threonine KinasesUp-RegulationConceptsHypertrophic responseMiR-182Myocardial hypertrophyEndothelial-cardiomyocyte crosstalkLV pressure overloadEndothelium-derived NOPlacental growth factorMyocardial hypertrophic responseDevelopment of hypertrophyDegradation of regulatorsMiR-182 targetsHemodynamic demandsPressure overloadPlGF expressionBlood supplyParacrine actionCardiomyocyte hypertrophyMyocardial angiogenesisCardiac angiogenesisTreatment inhibitsHypertrophyAKT/mTORC1 pathwaysNovel targetAkt/Growth factor
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 neovascularizationInterferon-&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
ELAVL1 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 angiogenesisThe vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury
Qi D, Atsina K, Qu L, Hu X, Wu X, Xu B, Piecychna M, Leng L, Fingerle-Rowson G, Zhang J, Bucala R, Young LH. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury. Journal Of Clinical Investigation 2014, 124: 3540-3550. PMID: 24983315, PMCID: PMC4109524, DOI: 10.1172/jci73061.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorContractile dysfunctionAntibody-dependent neutralizationAutocrine/paracrine effectsCoronary artery ligationCardiac contractile dysfunctionMigration inhibitory factorLV contractile dysfunctionDopachrome tautomeraseMolecular signaling pathwaysArtery ligationIschemic injuryCardiac sizeCardiomyocyte secretionControl heartsProtective effectKnockout miceParacrine effectsIschemic stressPhysiologic responsesInhibitory factorMore necrosisDysfunctionInjuryMurine cardiomyocytesNetrin-1 controls sympathetic arterial innervation
Brunet I, Gordon E, Han J, Cristofaro B, Broqueres-You D, Liu C, Bouvrée K, Zhang J, del Toro R, Mathivet T, Larrivée B, Jagu J, Pibouin-Fragner L, Pardanaud L, Machado MJ, Kennedy TE, Zhuang Z, Simons M, Levy BI, Tessier-Lavigne M, Grenz A, Eltzschig H, Eichmann A. Netrin-1 controls sympathetic arterial innervation. Journal Of Clinical Investigation 2014, 124: 3230-3240. PMID: 24937433, PMCID: PMC4071369, DOI: 10.1172/jci75181.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornDCC ReceptorFemaleGrowth ConesMaleMesenteric ArteriesMiceMice, KnockoutMice, Mutant StrainsMice, TransgenicModels, NeurologicalMyocytes, Smooth MuscleNerve Growth FactorsNetrin-1PregnancyReceptors, Cell SurfaceSympathetic Nervous SystemTumor Suppressor ProteinsVasoconstrictionConceptsSmooth muscle cellsArterial innervationNetrin-1Resistance arteriesAutonomic sympathetic nervesArterial smooth muscle cellsPeripheral resistance arteriesBlood flow regulationOnset of innervationBlood flow controlCell type-specific deletionAxon guidance cue netrin-1Guidance cue netrin-1Sympathetic nervesSympathetic innervationVascular toneColorectal cancerPeripheral organsSympathetic neuronsBlood supplyInnervationMuscle cellsSympathetic growth conesArteryGrowth cones
2013
Lipid lowering and imaging protease activation in atherosclerosis
Razavian M, Nie L, Challa A, Zhang J, Golestani R, Jung JJ, Robinson S, Sadeghi MM. Lipid lowering and imaging protease activation in atherosclerosis. Journal Of Nuclear Cardiology 2013, 21: 319-328. PMID: 24368425, PMCID: PMC3991560, DOI: 10.1007/s12350-013-9843-7.Peer-Reviewed Original ResearchConceptsHigh-fat dietLipid-lowering interventionsHFD groupPlaque inflammationAtherosclerotic miceMicroSPECT/CT imagingTotal blood cholesterolModern therapeutic approachesSmooth muscle αMMP tracerFat dietBlood cholesterolPlaque biologyTherapeutic approachesTracer uptakeMatrix metalloproteinaseTherapeutic interventionsAtherosclerosisActin expressionCT imagingMuscle αWeeksFenofibrateMiceInterventionAngiopoietin-2 Secretion by Endothelial Cell Exosomes REGULATION BY THE PHOSPHATIDYLINOSITOL 3-KINASE (PI3K)/Akt/ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) AND SYNDECAN-4/SYNTENIN PATHWAYS*
Ju R, Zhuang ZW, Zhang J, Lanahan AA, Kyriakides T, Sessa WC, Simons M. Angiopoietin-2 Secretion by Endothelial Cell Exosomes REGULATION BY THE PHOSPHATIDYLINOSITOL 3-KINASE (PI3K)/Akt/ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) AND SYNDECAN-4/SYNTENIN PATHWAYS*. Journal Of Biological Chemistry 2013, 289: 510-519. PMID: 24235146, PMCID: PMC3879572, DOI: 10.1074/jbc.m113.506899.Peer-Reviewed Original ResearchConceptsPI3K/Akt/endothelial nitric oxide synthaseAkt/endothelial nitric oxide synthaseAkt1 null miceCritical signaling pathwaysMode of secretionEndothelial nitric oxide synthaseExtracellular proteinsSignaling pathwaysSyndecan-4Angiopoietin/Tie2Novel mechanismVascular defectsNitric oxide synthaseAngiopoietin-2 secretionNull miceTie2 receptorPathwayPrincipal ligandEndothelial cellsSynthaseVascular integrityRegulationOxide synthaseVascular growthImportant roleTransmembrane 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
2010
Molecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo
Razavian M, Zhang J, Nie L, Tavakoli S, Razavian N, Dobrucki LW, Sinusas AJ, Edwards DS, Azure M, Sadeghi MM. Molecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo. Journal Of Nuclear Medicine 2010, 51: 1107-1115. PMID: 20554725, PMCID: PMC2908304, DOI: 10.2967/jnumed.110.075259.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EArteriovenous FistulaAutoradiographyCarotid ArteriesCatalysisDisease ProgressionEnzyme ActivationImmunohistochemistryIndicators and ReagentsMatrix MetalloproteinasesMiceMice, KnockoutRadiopharmaceuticalsReverse Transcriptase Polymerase Chain ReactionSubstrate SpecificityTomography, Emission-ComputedTomography, Emission-Computed, Single-PhotonConceptsMatrix metalloproteinase activationMMP activationAneurysm inductionMetalloproteinase activationSPECT/CTCurrent imaging modalitiesPathogenesis of aneurysmsSpecific MMP inhibitorsGroups of animalsMMP tracerMolecular imagingArterial aneurysmsAneurysm expansionFocal uptakeDeficient miceCarotid aneurysmsCarotid arteryApolipoprotein ETracer uptakeAneurysmsMajor causeMMP inhibitorsVessel areaImaging modalitiesWk