2022
Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes.
Chen M, Hu R, Cavinato C, Zhuang ZW, Zhang J, Yun S, Fernandez Tussy P, Singh A, Murtada SI, Tanaka K, Liu M, Fernández-Hernando C, Humphrey JD, Schwartz MA. Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes. Diabetes 2022, 71: 2020-2033. PMID: 35771994, PMCID: PMC9450851, DOI: 10.2337/db21-0958.Peer-Reviewed Original ResearchConceptsVascular complicationsInjection of streptozotocinBlood flow recoveryHigh-fat dietType 1 diabetesInflammatory cell invasionIntegrin α5T1D miceVascular basement membraneVascular diseaseCarotid arteryHindlimb ischemiaMetalloproteinase expressionMain receptorType 1Plaque sizeBeneficial effectsEndothelial cellsMajor causeCell invasionExtracellular matrix proteinsHyperlipidemiaComplicationsBasement membraneT1D
2021
Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling
Budatha M, Zhang J, Schwartz MA. Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling. Journal Of The American Heart Association 2021, 10: e021160. PMID: 34472370, PMCID: PMC8649308, DOI: 10.1161/jaha.121.021160.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionPathological vascular remodelingVascular remodelingCarotid ligation modelPartial carotid ligation modelAortic constrictionInflammatory activationEndothelial cellsLigation modelArtery wall hypertrophyTransverse aortic constriction (TAC) modelHigh-fat dietIntegrin α5Aortic constriction modelWild-type miceBasement membranePartial carotid ligationVascular endothelial cellsProvisional matrix proteinsAcute atherosclerosisHyperlipidemic ApoEInflammatory markersLigation surgeryWall hypertrophyAcute model
2017
Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta.
Misra A, Feng Z, Zhang J, Lou ZY, Greif DM. Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta. Journal Of Visualized Experiments 2017 PMID: 28930997, PMCID: PMC5752224, DOI: 10.3791/56039.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic smooth muscle cellsPregnant micePharmacological agentsAortic wallAortaLarge arteriesAdult aortaMuscle cellsEndothelial cellsPathological modelsHypothesis-generating experimentsContinuous exposureCell explantsTissue explantsPathogenesisFate mappingSpecific gene targetsClonal analysisNormal developmentVivoGene targetsExtracellular matrixClonal architectureCellsPKN1 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 activationCells
2016
Syndecan 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 vesselsExpressionVangl2RemodelingCellsMorphogenesis
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 neovascularization
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 angiogenesisPTP1b Is a Physiologic Regulator of Vascular Endothelial Growth Factor Signaling in Endothelial Cells
Lanahan AA, Lech D, Dubrac A, Zhang J, Zhuang ZW, Eichmann A, Simons M. PTP1b Is a Physiologic Regulator of Vascular Endothelial Growth Factor Signaling in Endothelial Cells. Circulation 2014, 130: 902-909. PMID: 24982127, PMCID: PMC6060619, DOI: 10.1161/circulationaha.114.009683.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCell MovementCell ProliferationDisease Models, AnimalEndothelial CellsFemaleHindlimbHuman Umbilical Vein Endothelial CellsIschemiaMaleMiceMice, Mutant StrainsNeovascularization, PhysiologicPrimary Cell CultureProtein Tyrosine Phosphatase, Non-Receptor Type 1RNA, Small InterferingSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsPhosphotyrosine phosphatase 1BVascular endothelial growth factor receptor 2 signalingExtracellular signal-regulated kinaseGrowth factor signalingVEGF-dependent activationSignal-regulated kinaseNull miceVascular endothelial growth factor signalingRegulation of angiogenesisEndothelial traffickingEndothelial-specific deletionFactor signalingEndothelial VEGFR2Phosphatase 1BEndothelial cellsKey regulatorReceptor 2 signalingVEGFR2 signalingSignalingImportant roleEndothelial knockoutPhysiologic regulatorHindlimb ischemia mouse modelRegulationImpaired blood flow recovery
2013
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*
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 roleEndothelial Cell–Dependent Regulation of Arteriogenesis
Moraes F, Paye J, 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