2024
mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis
Min W, Qin L, Zhang H, López-Giráldez F, Jiang N, Kim Y, Mohan V, Su M, Murray K, Grutzendler J, Zhou J. mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis. Circulation Research 2024, 135: e94-e113. PMID: 38957991, PMCID: PMC11293987, DOI: 10.1161/circresaha.123.324015.Peer-Reviewed Original ResearchCerebral vascular malformationsEndothelial progenitor cellsBlood-brain barrier integritySingle-cell RNA sequencing analysisDisruption of blood-brain barrier integrityBarrier integrityResident endothelial progenitor cellsRNA sequencing analysisTissue immunofluorescence analysisEndothelial cellsEPC clustersStem cell markersFocal neurological deficitsBrain's neurovascular unitMTOR signalingHuman CCM lesionsMTORC1 signalingBlood-brain barrierCapillary endothelial cellsCCM pathogenesisVascular malformationsLesion signaturesNeurological deficitsCell markersClonal expansion
2021
ATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells
Wang K, Chen H, Zhou Z, Zhang H, Zhou HJ, Min W. ATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells. Cell & Bioscience 2021, 11: 11. PMID: 33422124, PMCID: PMC7796565, DOI: 10.1186/s13578-020-00514-z.Peer-Reviewed Original ResearchActivation of mitophagyHuman umbilical vein endothelial cellsNormal mitochondrial structureMorphology of mitochondriaRNA-seq screeningMitochondrial membrane potentialCRISPR-Cas9 SystemCerebral cavernous malformationsEndothelial cellsExpression of KLF4Destruction of mitochondriaUmbilical vein endothelial cellsMitochondrial structureSignaling pathwaysVein endothelial cellsMitochondriaATPIF1MitophagyEndothelial progenitor cellsProgenitor cellsCell proliferationMembrane potentialKLF4PathwayProtein
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisBMX Represses Thrombin-PAR1–Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis
Li Z, Yin M, Zhang H, Ni W, Pierce R, Zhou HJ, Min W. BMX Represses Thrombin-PAR1–Mediated Endothelial Permeability and Vascular Leakage During Early Sepsis. Circulation Research 2020, 126: 471-485. PMID: 31910739, PMCID: PMC7035171, DOI: 10.1161/circresaha.119.315769.Peer-Reviewed Original ResearchConceptsPAR1 internalizationPuncture-induced sepsisCecal ligationVascular leakageEndothelial permeabilityExpression of BmxThrombin-PAR1Early sepsisEndothelial cellsPuncture modelSignal inactivationPAR1 antagonist SCH79797Negative regulatorLung epithelial cellsTransendothelial electrical resistanceAdult stageEmbryonic stagesCultured endothelial cellsPulmonary leakageCellular analysisLung injuryPathological stimuliEndothelium dysfunctionPlatelet dysfunctionSepsis
2019
Nuclear localization of the tyrosine kinase BMX mediates VEGFR2 expression
Liu T, Li Y, Su H, Zhang H, Jones D, Zhou HJ, Ji W, Min W. Nuclear localization of the tyrosine kinase BMX mediates VEGFR2 expression. Journal Of Cellular And Molecular Medicine 2019, 24: 126-138. PMID: 31642192, PMCID: PMC6933376, DOI: 10.1111/jcmm.14663.Peer-Reviewed Original ResearchConceptsTyrosine kinase BMXVEGFR2 promoter activityPromoter activityNuclear localizationVEGFR2 promoterKinase-inactive formGene promoter activityEndothelial cellsNucleus of ECsVascular endothelial growth factor receptorSiRNA-mediated silencingAngiogenesis-related diseasesChromatin immunoprecipitationDirect transactivationSH3 domainTranscription factorsGrowth factor receptorVEGFR2 expressionNovel functionVEGFR2 transcriptionSp1Human endothelial cellsLuciferase assayEC migrationFactor receptorShort AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction
Li Z, Li L, Zhang H, Zhou HJ, Ji W, Min W. Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction. Arteriosclerosis Thrombosis And Vascular Biology 2019, 40: 112-127. PMID: 31619063, PMCID: PMC7204498, DOI: 10.1161/atvbaha.119.312976.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicApoptosisArteriosclerosisBlotting, WesternCells, CulturedDisease Models, AnimalDNAEndothelium, VascularGene Expression RegulationGenome-Wide Association StudyHumansMiceMice, Inbred C57BLMice, TransgenicMicroscopy, FluorescenceMitochondriaRas GTPase-Activating ProteinsSignal TransductionConceptsN-terminal pleckstrin homology domainHuman genome-wide association studiesGenome-wide association studiesPleckstrin homology domainMitochondrial reactive oxygen species generationEndothelial cellsH3K9 trimethylationHomology domainReactive oxygen species productionOxygen species productionReactive oxygen speciesReactive oxygen species generationAssociation studiesRegulatory factorsEpigenetic inhibitionEC activationOxygen species generationDependent pathwayVascular endothelial cellsProteolytic degradationSpecies productionOxygen speciesVascular homeostasisMitochondriaSpecies generation
2018
SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis
Zhou HJ, Xu Z, Wang Z, Zhang H, Zhuang Z, Simons M, Min W. SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological angiogenesis. Nature Communications 2018, 9: 3303. PMID: 30120232, PMCID: PMC6098000, DOI: 10.1038/s41467-018-05812-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCorneaCysteine EndopeptidasesDiabetes MellitusEndopeptidasesGene DeletionGene Knock-In TechniquesGene SilencingGolgi ApparatusHuman Umbilical Vein Endothelial CellsHumansIntracellular SpaceMaleMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicProtein TransportRetinaSignal TransductionSUMO-1 ProteinSumoylationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsPathological angiogenesisPotential therapeutic targetRegulation of VEGFR2Non-sumoylated formEndothelial-specific deletionDiabetic miceHindlimb ischemiaTherapeutic targetDiabetic settingControl of angiogenesisEndothelial cellsAngiogenesisVEGFR2Surface expressionVEGFR2 activityTissue repairSENP1Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
Zhang J, Chen C, Li L, Zhou HJ, Li F, Zhang H, Yu L, Chen Y, Min W. Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2. Frontiers In Physiology 2018, 9: 396. PMID: 29731721, PMCID: PMC5921534, DOI: 10.3389/fphys.2018.00396.Peer-Reviewed Original ResearchIntima-media thickeningVascular smooth muscle cellsEarly time pointsCytosolic subunit p47phoxLigation modelVascular remodelingReactive oxygen speciesVessel dysfunctionIntima/media ratioNOX2 complexMouse carotid artery ligation modelEndothelial cellsSubunit p47phoxCarotid artery ligation modelTime pointsNADPH oxidase 2Artery ligation modelROS productionHuman atherosclerotic plaquesSmooth muscle cellsCarotid ligation modelVSMC accumulationIntima areaApoE-KO mouse modelVascular disease
2017
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway
Sun Y, Zhang H, Xing X, Zhao Z, He J, Li J, Chen J, Wang M, He Y. Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway. Journal Of Developmental Origins Of Health And Disease 2017, 9: 182-190. PMID: 29110746, DOI: 10.1017/s2040174417000782.Peer-Reviewed Original ResearchConceptsMouse embryosYolk sacHeterozygous mouse embryosGene defectsCCM3 genesPrimary human umbilical vein endothelial cellsLead exposureMitochondrial DNAEmbryonic developmentMtDNA biogenesisMitochondrial morphologyCardiovascular developmentHuman umbilical vein endothelial cellsMitochondrial pathwayGene knockoutEndothelial cellsUmbilical vein endothelial cellsVascular developmentMitochondria pathwayVein endothelial cellsPrimary cellsGenesRNA expressionCell proliferationEmbryosThe critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis
Qiu C, Wang Y, Zhao H, Qin L, Shi Y, Zhu X, Song L, Zhou X, Chen J, Zhou H, Zhang H, Tellides G, Min W, Yu L. The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis. Nature Communications 2017, 8: 15426. PMID: 28569748, PMCID: PMC5461500, DOI: 10.1038/ncomms15426.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriosclerosisCysteine EndopeptidasesDisease ProgressionDNAEndopeptidasesEndothelial CellsEndothelium, VascularGATA2 Transcription FactorHuman Umbilical Vein Endothelial CellsHumansInflammation MediatorsLeukocytesMaleMice, Inbred C57BLMice, KnockoutModels, BiologicalProtein BindingProtein StabilitySumoylationConceptsGraft arteriosclerosisEndothelial activationClinical graft rejectionConsequent endothelial dysfunctionNF-κB activityRole of SENP1Post-translational SUMOylationAllograft failureEndothelial dysfunctionGraft rejectionGraft endotheliumLeukocyte recruitmentVascular remodellingCardiovascular disordersNeointima formationNF-κBClinical researchDiminished inductionEndothelial cellsMajor causeAdhesion moleculesPotential involvementInflammationArteriosclerosisSENP1
2015
AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis
Ji W, Li Y, He Y, Yin M, Zhou HJ, Boggon TJ, Zhang H, Min W. AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis. Cancer Research 2015, 75: 3492-3504. PMID: 26139244, PMCID: PMC4558200, DOI: 10.1158/0008-5472.can-15-0088.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBreast NeoplasmsCarrier ProteinsCell Line, TumorEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGuanylate KinasesHumansMelanoma, ExperimentalMiceNeoplasm MetastasisNeovascularization, PathologicProtein Kinase InhibitorsSignal TransductionTumor MicroenvironmentVascular Endothelial Growth Factor Receptor-2ConceptsEpithelial-mesenchymal transitionPremetastatic niche formationTumor growthAugments tumor growthBreast cancer modelSuppresses tumor progressionVascular endothelial cellsNiche formationSystemic administrationCancer modelVEGFR2 kinase inhibitorTumor neovascularizationTumor progressionTumor angiogenesisTumor microenvironmentTumor cellsEndothelial cellsMetastasisKinase inhibitorsTumor nicheVascular ECsSpecific deletionVascular environmentEMT switchAIP1 gene
2014
AIP1 Mediates Vascular Endothelial Cell Growth Factor Receptor-3–Dependent Angiogenic and Lymphangiogenic Responses
Zhou HJ, Chen X, Huang Q, Liu R, Zhang H, Wang Y, Jin Y, Liang X, Lu L, Xu Z, Min W. AIP1 Mediates Vascular Endothelial Cell Growth Factor Receptor-3–Dependent Angiogenic and Lymphangiogenic Responses. Arteriosclerosis Thrombosis And Vascular Biology 2014, 34: 603-615. PMID: 24407031, PMCID: PMC3952062, DOI: 10.1161/atvbaha.113.303053.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCells, CulturedCorneaEndocytosisEndothelial CellsEndothelium, VascularEye ProteinsGuanylate KinasesHumansLymphangiogenesisMiceMice, KnockoutMicroRNAsNeuronsRas GTPase-Activating ProteinsReceptors, NotchRecombinant ProteinsRetinal NeovascularizationRNA InterferenceRNA, Small InterferingVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3ConceptsLymphatic endothelial cellsASK1-interacting protein-1VEGFR-3 signalingHuman lymphatic endothelial cellsVEGFR-3Vascular endothelial cell growth factor receptorEndothelial cellsReduced expressionDevelopmental lymphangiogenesisScaffold proteinAIP1 functionsGrowth factor receptorLymphangiogenic signalingNovel functionVEGFR-2 activityRNA knockdownCell growth factor receptorLymphangiogenic responseSimilar defectsFirst insightProtein 1Vascular endothelial cellsPathological angiogenesisSpecific deletionFactor receptor
2013
SOCS1 Prevents Graft Arteriosclerosis by Preserving Endothelial Cell Function
Qin L, Huang Q, Zhang H, Liu R, Tellides G, Min W, Yu L. SOCS1 Prevents Graft Arteriosclerosis by Preserving Endothelial Cell Function. Journal Of The American College Of Cardiology 2013, 63: 21-29. PMID: 23994402, PMCID: PMC3932325, DOI: 10.1016/j.jacc.2013.08.694.Peer-Reviewed Original ResearchConceptsAdhesion molecule-1Cell adhesion molecule-1Graft arteriosclerosisMolecule-1Aortic endothelial cellsEndothelial cellsEndothelial functionGA progressionNeointima formationLate cardiac allograft failureVascular cell adhesion molecule-1Intercellular adhesion molecule-1Cytokine-induced adhesion molecule expressionCardiac allograft failureNormal endothelial functionEndothelial inflammatory responseInflammatory cell infiltrationMouse aortic endothelial cellsAdhesion molecule expressionPlatelet/endothelial cell adhesion molecule-1Better vascular functionEndothelial cell adhesion molecule-1Cytokine-induced expressionEndothelial adhesion moleculesCultured aortic endothelial cells
2011
AIP1 Prevents Graft Arteriosclerosis by Inhibiting Interferon-&ggr;–Dependent Smooth Muscle Cell Proliferation and Intimal Expansion
Yu L, Qin L, Zhang H, He Y, Chen H, Pober JS, Tellides G, Min W. AIP1 Prevents Graft Arteriosclerosis by Inhibiting Interferon-&ggr;–Dependent Smooth Muscle Cell Proliferation and Intimal Expansion. Circulation Research 2011, 109: 418-427. PMID: 21700930, PMCID: PMC3227522, DOI: 10.1161/circresaha.111.248245.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, AbdominalAorta, ThoracicArteriosclerosisCell MovementCell ProliferationCells, CulturedDisease Models, AnimalHumansInterferon-gammaJanus Kinase 2MaleMiceMice, KnockoutMinor Histocompatibility AntigensMuscle, Smooth, VascularRas GTPase-Activating ProteinsReceptors, InterferonSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorTime FactorsTunica IntimaVascular GraftingConceptsASK1-interacting protein-1Neointima formationTransplantation modelIntimal expansionSingle minor histocompatibility antigenSmooth muscle cell proliferationMinor histocompatibility antigensAortic transplantation modelAorta transplantation modelMuscle cell proliferationVSMC accumulationDonor graftsGraft arteriosclerosisIntimal formationIntravenous administrationHistocompatibility antigensVSMC proliferationMouse aortaVSMC migrationIFNProliferative diseasesEndothelial cellsProtein 1Cell proliferationJAK-STAT signaling
2009
JAK2 and SHP2 Reciprocally Regulate Tyrosine Phosphorylation and Stability of Proapoptotic Protein ASK1*
Yu L, Min W, He Y, Qin L, Zhang H, Bennett AM, Chen H. JAK2 and SHP2 Reciprocally Regulate Tyrosine Phosphorylation and Stability of Proapoptotic Protein ASK1*. Journal Of Biological Chemistry 2009, 284: 13481-13488. PMID: 19287004, PMCID: PMC2679448, DOI: 10.1074/jbc.m809740200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell LineEndothelial CellsEnzyme StabilityHumansInterferon-gammaJanus Kinase 2MAP Kinase Kinase Kinase 5MiceMice, KnockoutMultienzyme ComplexesMutationPhosphorylationProtein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTumor Necrosis Factor-alphaConceptsTyrosine phosphorylationSubstrate-trapping mutantProtein tyrosine phosphatase 2Phosphatase-inactive mutantProteasomal inhibitor MG132ASK1-JNK signalingEndothelial cellsJAK2-specific inhibitorIFN-gamma-induced tyrosine phosphorylationASK1 degradationASK1 dephosphorylationInactive mutantMouse endothelial cellsASK1 phosphorylationPhosphatase 2Inhibitor MG132SHP2Wild typeASK1DephosphorylationMutantsPhosphorylationEnhanced associationJAK2EC apoptosisEndothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis
Dai S, He Y, Zhang H, Yu L, Wan T, Xu Z, Jones D, Chen H, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis. Arteriosclerosis Thrombosis And Vascular Biology 2009, 29: 495-502. PMID: 19150880, PMCID: PMC2734510, DOI: 10.1161/atvbaha.108.180349.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArteriesBlood Flow VelocityCell MovementDisease Models, AnimalEndothelial CellsHindlimbIschemiaJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase Kinase 5MiceMice, TransgenicMitochondriaMuscle, SkeletalNeovascularization, PhysiologicNitric OxideOxidative StressReactive Oxygen SpeciesRegional Blood FlowSignal TransductionThioredoxinsTime FactorsConceptsEndothelial cellsFlow recoveryFemoral artery ligation modelIschemia-mediated arteriogenesisIschemic reserve capacityLimb perfusion recoveryENOS-deficient miceENOS-KO miceNitric oxide bioavailabilityIschemia-induced angiogenesisEC apoptosisArtery ligation modelEC survivalENOS deletionNontransgenic littermatesStress-induced activationLigation modelPerfusion recoveryLower limbsUpper limbEndothelial-specific expressionSevere impairmentMajor antioxidant proteinsIschemiaMice
2008
AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor–Induced ASK1-JNK Activation
Min W, Lin Y, Tang S, Yu L, Zhang H, Wan T, Luhn T, Fu H, Chen H. AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor–Induced ASK1-JNK Activation. Circulation Research 2008, 102: 840-848. PMID: 18292600, DOI: 10.1161/circresaha.107.168153.Peer-Reviewed Original ResearchConceptsASK1-JNK signalingASK1 dephosphorylationAssociation of PP2APP2A catalytic subunitCatalytic inactive formPP2A inhibitor okadaicASK1-JNK activationC-Jun N-terminal kinaseActivation of JNKEndothelial cellsN-terminal kinasePhosphatase PP2ACritical rolePotential phosphataseProtein phosphataseGAP domainInhibitor okadaicProtein familyCatalytic subunitC2 domainPP2AAIP1Novel memberApoptotic signalingRNA knockdownSENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis
Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death & Differentiation 2008, 15: 739-750. PMID: 18219322, DOI: 10.1038/sj.cdd.4402303.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsApoptosisCarrier ProteinsCattleCells, CulturedCysteine EndopeptidasesCytoplasmEndopeptidasesEndothelial CellsFibroblastsHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMutationProtein KinasesProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProtein TransportReactive Oxygen SpeciesRecombinant ProteinsRNA InterferenceRNA, Small InterferingSignal TransductionSmall Ubiquitin-Related Modifier ProteinsThioredoxinsTime FactorsTransfectionTumor Necrosis Factor-alphaConceptsASK1-dependent apoptosisASK1-JNK activationCytoplasmic translocationMouse embryonic fibroblast cellsNuclear translocationSUMO-specific proteasesWild-type formEmbryonic fibroblast cellsNuclear importAntioxidant protein thioredoxinHIPK1Mutant formsEndothelial cellsDeSUMOylationProtein thioredoxinSubsequent cytoplasmic translocationSENP1TranslocationCritical functionsThioredoxinFibroblast cellsApoptosisCellsActivationSUMO
2007
RIP1-mediated AIP1 Phosphorylation at a 14-3-3-binding Site Is Critical for Tumor Necrosis Factor-induced ASK1-JNK/p38 Activation*
Zhang R, Zhang H, Lin Y, Li J, Pober JS, Min W. RIP1-mediated AIP1 Phosphorylation at a 14-3-3-binding Site Is Critical for Tumor Necrosis Factor-induced ASK1-JNK/p38 Activation*. Journal Of Biological Chemistry 2007, 282: 14788-14796. PMID: 17389591, DOI: 10.1074/jbc.m701148200.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAdaptor Proteins, Signal TransducingAmino Acid SubstitutionAnimalsApoptosisCarrier ProteinsCattleCells, CulturedEndothelial CellsEnzyme ActivationGuanylate KinasesHumansMAP Kinase Kinase 4MAP Kinase Kinase Kinase 5MAP Kinase Signaling SystemMultiprotein ComplexesMutation, MissenseP38 Mitogen-Activated Protein KinasesPhosphorylationProtein BindingProtein Processing, Post-TranslationalProteinsReceptor-Interacting Protein Serine-Threonine KinasesTNF Receptor-Associated Factor 2Tumor Necrosis Factor-alphaConceptsJNK/p38 activationP38 activationTRAF2-ASK1ASK1-JNK activationPhospho-specific antibodiesTNF treatmentEndothelial cellsComplex formationGAP domainProtein familyTerminal domainAIP1Novel memberApoptotic signalingTNF signalingRNA knockdownRIP1PhosphorylationProtein 1ASK1-interacting protein-1EC apoptosisTRAF2ASK1Similar kineticsTumor necrosis factorEndothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions
Zhang H, Luo Y, Zhang W, He Y, Dai S, Zhang R, Huang Y, Bernatchez P, Giordano FJ, Shadel G, Sessa WC, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Improves Endothelial Cell Function and Reduces Atherosclerotic Lesions. American Journal Of Pathology 2007, 170: 1108-1120. PMID: 17322393, PMCID: PMC1864879, DOI: 10.2353/ajpath.2007.060960.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaApolipoproteins EAtherosclerosisCells, CulturedEndothelial CellsFlow CytometryImmunoblottingImmunohistochemistryMiceMice, TransgenicMicroscopy, ConfocalMitochondrial ProteinsNitric OxideReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionThioredoxinsVasodilationConceptsTg miceAtherosclerotic lesionsOxidative stressNitric oxide levelsEC functionDeficient mouse modelEndothelial cell functionAtherosclerosis developmentEnhanced vasodilationVascular EC functionEndothelium functionApolipoprotein EControl littermatesMouse modelOxide levelsMice showCapacity of ECEndothelial-specific expressionEndothelial cellsCritical roleReactive oxygen speciesCell functionMiceTotal antioxidantsLesions