2023
Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension
Zhou X, Jiang Y, Wang Y, Fan L, Zhu Y, Chen Y, Wang Y, Zhu Y, Wang H, Pan Z, Li Z, Zhu X, Ren R, Ge Z, Lai D, Lai E, Chen T, Wang K, Liang P, Qin L, Liu C, Qiu C, Simons M, Yu L. Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension. Circulation Research 2023, 133: 508-531. PMID: 37589160, DOI: 10.1161/circresaha.122.321200.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionHypoxic pulmonary hypertensionPulmonary endothelial functionHuman pulmonary artery endothelial cellsPulmonary artery endothelial cellsPulmonary endotheliumArtery endothelial cellsEndothelial functionEndothelial cellsEndothelial mitochondriaSugen/hypoxia rat modelClinical specimensPulmonary endothelial dysfunctionHypoxia rat modelPulmonary arterial systemHypoxic stressVascular remodeling diseasePrevious clinical researchHuman embryonic stem cell-derived endothelial cellsMitochondrial oxygen consumption rateIntrinsic pathogenesisEndothelial dysfunctionExtracellular acidification rateHypoxic ratsPoor prognosisChylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption
Zarkada G, Chen X, Zhou X, Lange M, Zeng L, Lv W, Zhang X, Li Y, Zhou W, Liu K, Chen D, Ricard N, Liao J, Kim Y, Benedito R, Claesson-Welsh L, Alitalo K, Simons M, Ju R, Li X, Eichmann A, Zhang F. Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption. Circulation Research 2023, 133: 333-349. PMID: 37462027, PMCID: PMC10530007, DOI: 10.1161/circresaha.123.322607.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsCell-cell junctionsCytoskeleton contractionMolecular biology approachesSmall GTPase Rac1Cytoskeletal contractilityBiology approachGTPase Rac1Stress fibersA SignalingPI3KLipid uptakePermeability regulationLymphatic permeabilityIntestinal lipid absorptionLEC junctionJunction openingEndothelial cellsLymphatic capillariesVEGFR-2Fundamental mechanismsLymphatic barrierLymphatic vesselsVascular endothelial growthLymphatic junctionsAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsEndotheliumHumansSignal TransductionTransforming Growth Factor betaVascular DiseasesConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4
2014
PTP1b 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 recoveryThe docking protein FRS2α is a critical regulator of VEGF receptors signaling
Chen PY, Qin L, Zhuang ZW, Tellides G, Lax I, Schlessinger J, Simons M. The docking protein FRS2α is a critical regulator of VEGF receptors signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 5514-5519. PMID: 24706887, PMCID: PMC3992672, DOI: 10.1073/pnas.1404545111.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCell MovementDNA PrimersEndothelial CellsGene Expression ProfilingGenetic VectorsHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansImmunoblottingImmunohistochemistryImmunoprecipitationLaser-Doppler FlowmetryLentivirusMembrane ProteinsMiceReal-Time Polymerase Chain ReactionReceptors, Vascular Endothelial Growth FactorSignal TransductionX-Ray MicrotomographyConceptsLymphatic endothelial cell migrationFibroblast growth factor receptor substrate 2Growth factor receptor substrate 2Cognate receptor tyrosine kinasesFactor receptor substrate 2Receptor kinase signalingVascular endothelial growth factorPostnatal vascular developmentReceptor tyrosine kinasesEndothelial cell migrationKinase signalingEndothelial-specific deletionAdult angiogenesisVEGF receptorsTyrosine kinaseCritical regulatorVascular developmentFRS2αSubstrate 2Cell migrationDependent activationCritical roleUnidentified componentsGrowth factorEndothelial growth factor
2013
Endothelial 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
2012
Endothelial Nuclear Factor-&kgr;B–Dependent Regulation of Arteriogenesis and Branching
Tirziu D, Jaba IM, Yu P, Larrivée B, Coon BG, Cristofaro B, Zhuang ZW, Lanahan AA, Schwartz MA, Eichmann A, Simons M. Endothelial Nuclear Factor-&kgr;B–Dependent Regulation of Arteriogenesis and Branching. Circulation 2012, 126: 2589-2600. PMID: 23091063, PMCID: PMC3514045, DOI: 10.1161/circulationaha.112.119321.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBecaplerminBrainDisease Models, AnimalEndothelial CellsHindlimbHuman Umbilical Vein Endothelial CellsHumansHypoxia-Inducible Factor 1, alpha SubunitIschemiaMiceMice, TransgenicNeovascularization, PathologicNeovascularization, PhysiologicNF-kappa B p50 SubunitProto-Oncogene Proteins c-sisRetinaVascular Endothelial Growth Factor AConceptsNuclear factor-κB activationCollateral formationReduced adhesion molecule expressionHypoxia-inducible factor-1α levelsDistal tissue perfusionVascular endothelial growth factorAdhesion molecule expressionPlatelet-derived growth factor-BBEndothelial growth factorGrowth factor-BBMolecule expressionMonocyte influxCollateral networkTissue perfusionImmature vesselsArterial networkBaseline levelsNFκB activationNuclear factorFactor-BBGrowth factor