Featured Publications
Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMiceSUMOylation 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 repairSENP1Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Huang Q, Zhou HJ, Zhang H, Huang Y, Hinojosa-Kirschenbaum F, Fan P, Yao L, Belardinelli L, Tellides G, Giordano FJ, Budas GR, Min W. Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function. Circulation 2015, 131: 1082-1097. PMID: 25628390, PMCID: PMC4374031, DOI: 10.1161/circulationaha.114.012725.Peer-Reviewed Original ResearchConceptsMitochondrial reactive oxygen species generationReactive oxygen species generationOxygen species generationASK1-dependent apoptosisMitochondrial reactive oxygen species productionPhosphorylation/activityKey mitochondrial proteinsSpecies generationMitochondrial membrane depolarizationKinase 1 activityMitochondrial proteinsReactive oxygen species productionCellular redoxMitochondrial Trx2Inhibition of ASK1Apoptotic signalingOxygen species productionThioredoxin 2Protein expression levelsKinase 1ATP productionASK1 inhibitionKnockout miceMitochondrial ultrastructureASK1 inhibitorsAIP1 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
2024
SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling
Xu Y, Zhang H, Chen Y, Pober J, Zhou M, Zhou J, Min W. SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling. Nature Communications 2024, 15: 6919. PMID: 39134547, PMCID: PMC11319592, DOI: 10.1038/s41467-024-51350-5.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSerum response factorCardiovascular diseaseVSMC synthetic phenotypeVascular remodelingNeointimal formationSENP1 deficiencySerum response factor activitySmooth muscle phenotypic switchingPhenotypic switchingPathogenesis of cardiovascular diseaseSmooth muscle cellsPost-translational SUMOylationTreatment of cardiovascular diseasesInhibitor AZD6244Phospho-ELK1Increased nuclear accumulationLysosomal localizationGene transcriptionNuclear accumulationMuscle cellsCoronary arteryCVD patientsVSMC phenotypic switchTherapeutic potential
2020
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. Journal Of Experimental Medicine 2020, 218: e20201416. PMID: 33315085, PMCID: PMC7927432, DOI: 10.1084/jem.20201416.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAnimalsDiabetes Mellitus, Type 2Diet, High-FatEnergy MetabolismFatty LiverGene DeletionGene TargetingGluconeogenesisHomeostasisHumansHyperglycemiaInflammationInsulin ResistanceLipogenesisLiverMaleMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative StressPhenotypeReactive Oxygen SpeciesSequestosome-1 ProteinSignal TransductionThioredoxinsConceptsHepatic insulin resistanceWhite adipose tissueInsulin resistanceAdipose inflammationType 2 diabetes mellitusLipid metabolic disordersNF-κB inhibitorAdipose-specific deletionWhole-body energy homeostasisAltered fatty acid metabolismFatty acid metabolismT2DM progressionT2DM patientsDiabetes mellitusReactive oxygen species pathwayHepatic steatosisMetabolic disordersNF-κBP62/SQSTM1Adipose tissueHuman adipocytesEnergy homeostasisExcessive mitophagyOxygen species pathwayInflammationMural 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
Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome
Yang B, Huang Y, Zhang H, Huang Y, Zhou HJ, Young L, Xiao H, Min W. Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome. Journal Of Molecular And Cellular Cardiology 2019, 138: 291-303. PMID: 31751569, DOI: 10.1016/j.yjmcc.2019.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBradycardiaCardiomyopathy, DilatedEnhancer Elements, GeneticHistone DeacetylasesHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMEF2 Transcription FactorsMice, KnockoutMitochondria, HeartModels, BiologicalOxidative StressPhenotypeProtein BindingReactive Oxygen SpeciesRNA, MessengerSick Sinus SyndromeSinoatrial NodeThioredoxinsConceptsSick sinus syndromeSinus syndromeHistone deacetylase 4Lower heart rateHeart rateHCN4 expressionConduction systemSinoatrial nodeNormal heart rateCardiac conduction systemHistone 3 acetylationMitochondrial oxidative stressSinus bradycardiaCardiac functionLox/SyndromeHeart rhythmMyosin heavy chainHistological analysisMiceDeletion miceOxidative stressWhole heartProtein levelsUnderlying mechanism
2017
ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis
Yin M, Zhou HJ, Zhang J, Lin C, Li H, Li X, Li Y, Zhang H, Breckenridge DG, Ji W, Min W. ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis. JCI Insight 2017, 2: e91828. PMID: 28931753, PMCID: PMC5621912, DOI: 10.1172/jci.insight.91828.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesOvarian cancer growthOvarian cancerTranscoelomic metastasisCancer growthTumor growthOrthotopic ovarian cancer modelPeritoneal tumor growthInflammation-mediated tumorigenesisOvarian cancer modelEndothelial cell activationJunction protein VE-cadherinOvarian cancer progressionTAM infiltrationMacrophage infiltrationVascular leakageMacrophage transmigrationVascular permeabilityMouse modelVascular endotheliumMetastasis cancerTherapeutic targetMacrophage activationColon cancerCancer model
2013
AIP1 Suppresses Atherosclerosis by Limiting Hyperlipidemia-Induced Inflammation and Vascular Endothelial Dysfunction
Huang Q, Qin L, Dai S, Zhang H, Pasula S, Zhou H, Chen H, Min W. AIP1 Suppresses Atherosclerosis by Limiting Hyperlipidemia-Induced Inflammation and Vascular Endothelial Dysfunction. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 795-804. PMID: 23413429, PMCID: PMC3637885, DOI: 10.1161/atvbaha.113.301220.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortic DiseasesApolipoproteins EAtherosclerosisBiomarkersBone Marrow TransplantationCholesterolCytokinesDisease Models, AnimalDose-Response Relationship, DrugEndothelium, VascularGene Expression RegulationHyperlipidemiasInflammationInflammation MediatorsLipoproteinsLipoproteins, LDLMacrophagesMiceMice, KnockoutNF-kappa BRas GTPase-Activating ProteinsSignal TransductionTriglyceridesVasoconstrictionVasoconstrictor AgentsVasodilationVasodilator AgentsConceptsInflammatory responseAtherosclerotic lesionsAortic ECsNuclear factor-κB (NF-κB) activityVascular endothelial dysfunctionPlasma inflammatory cytokinesWestern-type dietTotal cholesterol levelsIncreased inflammatory responseNuclear factor-κB signalingEndothelial cell dysfunctionAccumulation of macrophagesDouble knockout miceFactor-κB signalingNull mouse modelEndothelial dysfunctionProinflammatory mediatorsSuppresses AtherosclerosisControl miceInflammatory moleculesLipoprotein profileInflammatory cytokinesCholesterol levelsAortic rootEC dysfunctionFunctional Analyses of TNFR2 in Physiological and Pathological Retina AngiogenesisTNFR2 Mediates Retinal Angiogenesis
Wan T, Xu Z, Zhou HJ, Zhang H, Luo Y, Li Y, Min W. Functional Analyses of TNFR2 in Physiological and Pathological Retina AngiogenesisTNFR2 Mediates Retinal Angiogenesis. Investigative Ophthalmology & Visual Science 2013, 54: 211-221. PMID: 23188724, PMCID: PMC3544528, DOI: 10.1167/iovs.12-10364.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-2AnimalsAnimals, NewbornCell SurvivalDisease Models, AnimalEndothelium, VascularEpithelial CellsGene ExpressionHumansHypoxiaInfant, NewbornMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNeovascularization, PathologicNF-kappa BOxygenProtein-Tyrosine KinasesReceptor, TIE-2Receptors, Tumor Necrosis Factor, Type IIRetinaRetinal NeovascularizationRetinopathy of PrematurityVascular Endothelial Growth Factor Receptor-2ConceptsTumor necrosis factor receptor 2Wild-type C57BL/6 miceTNFR2 deletionTNFR2-KOOIR modelOxygen-induced retinopathy modelNecrosis factor receptor 2Pathological neovascular tuftsRetinal vascular repairVascular ECsRetinal vascular developmentIschemia-induced revascularizationRetinal vasculature developmentFactor receptor 2Vascular endothelial cellsPreretinal neovascularizationVascular developmentC57BL/6 miceNeovascular tuftsKO miceNeonatal miceIsolectin stainingVascular repairBone marrow kinasePostnatal day