Featured Publications
Endothelial Cell-Pericyte Interactions in the Pathogenesis of Cerebral Cavernous Malformations (CCMs).
Min W, Zhou JH. Endothelial Cell-Pericyte Interactions in the Pathogenesis of Cerebral Cavernous Malformations (CCMs). Cold Spring Harbor Perspectives In Medicine 2022, 13: a041188. PMID: 35667709, PMCID: PMC9760308, DOI: 10.1101/cshperspect.a041188.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsEndothelial cellsCavernous malformationsEndothelial cell-pericyte interactionsEC-specific deletionBrain vasculatureMice resultsLesion formationParenchymal cellsCCM formationLesionsPericytesPrimary defectFunction mutationsMalformationsUnexpected findingCell typesUbiquitous expressionCellsPatientsCaveolae-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 microscopyTie2PathogenesisMiceEndothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation
Zhou HJ, Qin L, Zhang H, Tang W, Ji W, He Y, Liang X, Wang Z, Yuan Q, Vortmeyer A, Toomre D, Fuh G, Yan M, Kluger MS, Wu D, Min W. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1033-1042. PMID: 27548575, PMCID: PMC5014607, DOI: 10.1038/nm.4169.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-1Angiopoietin-2AnimalsApoptosis Regulatory ProteinsBrainEndothelium, VascularEnzyme-Linked Immunosorbent AssayExocytosisFluorescent Antibody TechniqueGene Expression ProfilingHemangioma, Cavernous, Central Nervous SystemHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNerve Tissue ProteinsProto-Oncogene ProteinsReceptor, TIE-2Vesicle-Associated Membrane Protein 3SUMOylation 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 formationPathogenesis
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 generationCCM3 and cerebral cavernous malformation disease
Wang K, Zhou HJ, Min W. CCM3 and cerebral cavernous malformation disease. Stroke And Vascular Neurology 2019, 4: svn-2018-000195. PMID: 31338212, PMCID: PMC6613868, DOI: 10.1136/svn-2018-000195.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCapillary PermeabilityCell MovementCell ProliferationCerebral ArteriesEndothelial CellsGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMembrane ProteinsMutationNeovascularization, PathologicPhenotypeProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsSmall blood vesselsTreatment of CCMsCerebral cavernous malformation diseaseBlood vesselsRisk of strokeUnique biological functionsPotential therapeutic strategyFocal neurological defectsCCM proteinsEndothelial cell junctionsCCM3/Vascular lesionsBiological functionsDifferent genesCCM genesCavernous malformationsSevere formTherapeutic strategiesCell junctionsNeurological defectsSimilar functionsMalformation diseaseCCM diseaseDiseaseCritical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation
Xiang Q, Yang B, Li L, Qiu B, Qiu C, Gao X, Zhou H, Min W. Critical role of Lin28‐TNFR2 signalling in cardiac stem cell activation and differentiation. Journal Of Cellular And Molecular Medicine 2019, 23: 0-0. PMID: 30734494, PMCID: PMC6433861, DOI: 10.1111/jcmm.14202.Peer-Reviewed Original ResearchConceptsCardiac stem cell activationStem cell activationHuman inducible pluripotent stem cellsCardiac stem cell differentiationCSC activationStem cell differentiationInducible pluripotent stem cellsPluripotent stem cellsCardiac progenitor cellsCritical roleActivation of TNFR2Factor RNACell activationProtein Lin28Cardiomyocyte proteinsCell differentiationStem cellsProgenitor cellsStem cell-based therapiesCSC differentiationProtein expressionDifferentiationCell-based therapiesExpressionActivation
2017
ASK family in cardiovascular biology and medicine
Liu T, Zhou HJ, Min W. ASK family in cardiovascular biology and medicine. Advances In Biological Regulation 2017, 66: 54-62. PMID: 29107568, PMCID: PMC5705453, DOI: 10.1016/j.jbior.2017.10.011.Peer-Reviewed Original ResearchConceptsProtein kinase signalsMAPK signal cascadeCellular functionsKinase signalsSignal cascadeCell survivalCardiovascular biologyASK1Signal pathwayKey moleculesNovel therapeutic strategiesPathwayCrucial roleASK3MAPKKKASK2Therapeutic strategiesCardiovascular pathophysiologyBiologyApoptosisMitogenRegulationCurrent reviewCascadeProliferationMechanistic Role of Thioredoxin 2 in Heart Failure
Chen C, Chen H, Zhou HJ, Ji W, Min W. Mechanistic Role of Thioredoxin 2 in Heart Failure. Advances In Experimental Medicine And Biology 2017, 982: 265-276. PMID: 28551792, DOI: 10.1007/978-3-319-55330-6_14.Peer-Reviewed Original ResearchConceptsThioredoxin 2ASK1-dependent apoptosisMechanistic roleMitochondrial reactive oxygen species generationCellular oxidative stressGlobal gene knockoutMitochondrial proteinsEmbryonic lethalityMitochondrial Trx2Gene knockoutKinase 1Reactive oxygen species generationTrx2Key mechanistic roleOxygen species generationCardiomyocyte apoptosisActive tissuesApoptosisCommon mechanismOxidative stressSpecies generationPromising targetHeart failureTherapeutic strategiesTreatment of DCM
2016
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/jci87252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErbB ReceptorsFemaleHeterograftsHumansIntercellular Adhesion Molecule-1Macrophage-1 AntigenMacrophagesMiceMice, NudeNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationOvarian NeoplasmsSpheroids, CellularVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsTumor-associated macrophagesOvarian cancerTranscoelomic metastasisTumor cellsICAM-1Mouse modelEpithelial ovarian cancerOvarian cancer growthOvarian cancer metastasisSpheroid formationOvarian cancer progressionVEGF/VEGFRTumor cell proliferationPharmacological blockadeMetastatic cancerColon cancerCancer growthMetastasisAntibody neutralizationTumor growthCancerClinical pathologyCancer metastasisCancer progressionΑMβ2 integrin
2015
Tetramethylpyrazine protects CoCl2-induced apoptosis in human umbilical vein endothelial cells by regulating the PHD2/HIF/1α-VEGF pathway
Yang C, Xu Y, Zhou H, Yang L, Yu S, Gao Y, Huang Y, Lu L, Liang X. Tetramethylpyrazine protects CoCl2-induced apoptosis in human umbilical vein endothelial cells by regulating the PHD2/HIF/1α-VEGF pathway. Molecular Medicine Reports 2015, 13: 1287-1296. PMID: 26676934, DOI: 10.3892/mmr.2015.4679.Peer-Reviewed Original ResearchAIP1 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 geneAIP1-Mediated Stress Signaling in Atherosclerosis and Arteriosclerosis
Zhang J, Zhou HJ, Ji W, Min W. AIP1-Mediated Stress Signaling in Atherosclerosis and Arteriosclerosis. Current Atherosclerosis Reports 2015, 17: 24. PMID: 25732743, PMCID: PMC5051342, DOI: 10.1007/s11883-015-0503-z.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesHuman genome-wide association studiesApoptosis signal-regulating kinase 1Signal-regulated kinases 1EC-specific deletionEndothelial cellsStress signalingEndoplasmic reticulum stressAIP1 functionsKinase 1Association studiesAIP1Human cardiovascular diseaseVascular endothelial cellsReticulum stressProteinGene variantsMouse modelDAB2IPSignalingInflammatory responseDeletionRegulationStressCells
2014
Carbamoylating Activity Associated with the Activation of the Antitumor Agent Laromustine Inhibits Angiogenesis by Inducing ASK1-Dependent Endothelial Cell Death
Ji W, Yang M, Praggastis A, Li Y, Zhou HJ, He Y, Ghazvinian R, Cincotta DJ, Rice KP, Min W. Carbamoylating Activity Associated with the Activation of the Antitumor Agent Laromustine Inhibits Angiogenesis by Inducing ASK1-Dependent Endothelial Cell Death. PLOS ONE 2014, 9: e103224. PMID: 25068797, PMCID: PMC4113355, DOI: 10.1371/journal.pone.0103224.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiocatalysisCarbamatesCattleCell DeathCells, CulturedEndothelial CellsHumansHydrazinesImmunoblottingIsocyanatesMAP Kinase Kinase Kinase 5Mitogen-Activated Protein Kinase 8Neovascularization, PhysiologicSignal TransductionSulfonamidesThioredoxin Reductase 1ThioredoxinsConceptsTrx reductase 1Non-apoptotic pathwaysEndothelial cellsKinase activityCys residuesASK1Endothelial cell deathReductase 1Cell deathInterstrand DNATrx1Reduced thioredoxinInduces dissociationCell lysatesInhibitor 14Role of methylWhole cellsInhibits angiogenesisInhibition of angiogenesisEC deathFree thiol groupsChloroethylating speciesTumor angiogenesisASK1-JNK/p38Cells