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 expressionCellsPatientsCCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling
Qin L, Zhang H, Li B, Jiang Q, Lopez F, Min W, Zhou JH. CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling. Arteriosclerosis Thrombosis And Vascular Biology 2021, 41: 2943-2960. PMID: 34670407, PMCID: PMC8613000, DOI: 10.1161/atvbaha.121.316707.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCells, CulturedEndothelial CellsEndothelium, LymphaticFemaleGene DeletionHemangioma, Cavernous, Central Nervous SystemHyperplasiaMaleMAP Kinase Signaling SystemMice, Inbred StrainsModels, AnimalNF-kappa BTranslocation, GeneticVascular Endothelial Growth Factor Receptor-3ConceptsLymphatic ECsLymphatic defectsCerebral cavernous malformationsPan-endothelial cellsGrowth factor receptorTranscriptional levelTransport assaysLymphatic hyperplasiaCCM genesLymphatic dysfunctionNuclear translocationGenesFactor receptorVEGFR3ERK1/2Nuclear factorDeletionEC proliferationInhibition of VEGFR3Dependent mannerVascular endothelial growth factor receptorEndothelial growth factor receptorEC deletionAbnormal valve structureKPNA2Caveolae-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 3
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 formationPathogenesis
2019
CCM3 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 diseaseDisease
2016
Erratum: Endothelial 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. Erratum: Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nature Medicine 2016, 22: 1502-1502. PMID: 27923033, DOI: 10.1038/nm1216-1502c.Peer-Reviewed Original Research