2023
Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src
Sjöberg E, Melssen M, Richards M, Ding Y, Chanoca C, Chen D, Nwadozi E, Pal S, Love D, Ninchoji T, Shibuya M, Simons M, Dimberg A, Claesson-Welsh L. Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src. Journal Of Clinical Investigation 2023, 133: e161366. PMID: 37651195, PMCID: PMC10575733, DOI: 10.1172/jci161366.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseRenal cell carcinomaAnti-tumor immunityVascular leakageT cellsEndothelial barrierClear cell renal cell carcinomaCell renal cell carcinomaRegulatory T cellsHelper T cellsNitric oxide synthaseImmune cell activationAntitumor immunityImmunosuppressive cytokinesPoor prognosisCell carcinomaPLCγ pathwayOxide synthaseVascular permeabilityB cellsActivation of PLCγCell activationTumor vesselsDecreased expressionCancer formsChylomicrons 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 ResearchMeSH KeywordsAnimalsCapillary PermeabilityChylomicronsEndothelial CellsLymphatic VesselsMiceMonomeric GTP-Binding ProteinsPhosphatidylinositol 3-KinasesVascular Endothelial Growth Factor AConceptsLymphatic 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 junctions
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 repairSENP1
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 recovery
2013
The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis
Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M. The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis. Developmental Cell 2013, 25: 156-168. PMID: 23639442, PMCID: PMC3774154, DOI: 10.1016/j.devcel.2013.03.019.Peer-Reviewed Original ResearchAnimalsArteriesCells, CulturedCytoplasmEndocytosisEndosomesEndothelium, VascularMAP Kinase Signaling SystemMiceMorphogenesisNeovascularization, PathologicNeuropilin-1PhosphorylationSignal TransductionTransferrinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vesicular Transport Proteins
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
2001
Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease
Henry T, Rocha-Singh K, Isner J, Kereiakes D, Giordano F, Simons M, Losordo D, Hendel R, Bonow R, Eppler S, Zioncheck T, Holmgren E, McCluskey E. Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease. American Heart Journal 2001, 142: 872-880. PMID: 11685177, DOI: 10.1067/mhj.2001.118471.Peer-Reviewed Original ResearchMeSH KeywordsCoronary CirculationCoronary DiseaseEndothelial Growth FactorsHumansLymphokinesNeovascularization, PhysiologicProtein IsoformsRecombinant ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsRecombinant human vascular endothelial growth factorVascular endothelial growth factorMyocardial perfusion imagingEndothelial growth factorHuman vascular endothelial growth factorPerfusion imagingTherapeutic angiogenesisRadionuclide myocardial perfusion imagingGrowth factorMinimal hemodynamic changesSequential intracoronary infusionsCoronary artery bypassStable exertional anginaDose-escalation trialPercutaneous coronary interventionCoronary artery diseaseReversible perfusion defectsSevere myocardial ischemiaFuture clinical trialsStress myocardial perfusion studyExertional anginaMyocardial perfusion studiesSurgical revascularizationArtery bypassEscalation trialExpression of vascular endothelial growth factor and its receptors is increased, but microvascular relaxation is impaired in patients after acute myocardial ischemia
Xu X, Li J, Simons M, Li J, Laham R, Sellke F. Expression of vascular endothelial growth factor and its receptors is increased, but microvascular relaxation is impaired in patients after acute myocardial ischemia. Journal Of Thoracic And Cardiovascular Surgery 2001, 121: 735-742. PMID: 11279416, DOI: 10.1067/mtc.2001.112340.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseBiomarkersBlotting, WesternCoronary Artery BypassCoronary CirculationCoronary VesselsDNA ProbesEndothelial Growth FactorsEnzyme InhibitorsFemaleGene ExpressionHeart AtriaHumansLymphokinesMaleMiddle AgedMyocardial IschemiaNitroarginineNitroprussidePrognosisProtein IsoformsReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorReceptors, Growth FactorReceptors, MitogenReceptors, Vascular Endothelial Growth FactorReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSubstance PVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVasodilationVasodilator AgentsConceptsVascular endothelial growth factorEndothelial growth factorAcute myocardial ischemiaGrowth factor receptor 1Vascular endothelial growth factor receptor 1Vascular endothelial growth factor receptorFactor receptor 1Endothelial growth factor receptorMyocardial ischemiaGrowth factorReceptor 1Growth factor receptorMicrovascular relaxationFactor receptorGrowth factor receptor 2Protein expressionCoronary bypass operationsEndothelial growth factor receptor 2Vascular endothelial growth factor receptor 2Rat myocardial infarction modelFactor receptor 2Human atrial tissueVascular endothelial growthMyocardial infarction modelMessenger RNA levelsTherapeutic angiogenesis in cardiology using protein formulations
Post M, Laham R, Sellke F, Simons M. Therapeutic angiogenesis in cardiology using protein formulations. Cardiovascular Research 2001, 49: 522-531. PMID: 11166265, DOI: 10.1016/s0008-6363(00)00216-9.Peer-Reviewed Original ResearchAnimalsClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicDisease Models, AnimalEndothelial Growth FactorsFibroblast Growth Factor 2Genetic TherapyGrowth SubstancesHumansInjectionsInjections, IntravenousMyocardial IschemiaNeovascularization, PhysiologicPericardiumPeripheral Vascular DiseasesVascular Endothelial Growth Factor AEfficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia
Sato K, Wu T, Laham R, Johnson R, Douglas P, Li J, Sellke F, Bunting S, Simons M, Post M. Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. Journal Of The American College Of Cardiology 2001, 37: 616-623. PMID: 11216988, DOI: 10.1016/s0735-1097(00)01144-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularInfusions, Intra-ArterialInfusions, IntravenousLymphokinesMaleMicrocirculationMyocardial ContractionMyocardial IschemiaSwineVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsChronic myocardial ischemiaMyocardial ischemiaL-NAMEIntracoronary groupBlood flowNitro-L-arginine methyl ester hydrochlorideNitric oxide synthase inhibitionEndothelial growth factor treatmentLeft circumflex coronary arteryDose-limiting hypotensionOxide synthase inhibitionCircumflex coronary arteryVascular endothelial growth factor treatmentMyocardial blood flowRegional myocardial functionGrowth factor treatmentVEGF-induced angiogenesisIntravenous groupConcomitant administrationMicrovascular functionIntracoronary infusionCollateral indexDifferent regimensCoronary arteryIntravenous infusion
2000
Clinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus
Simons M, Bonow R, Chronos N, Cohen D, Giordano F, Hammond H, Laham R, Li W, Pike M, Sellke F, Stegmann T, Udelson J, Rosengart T. Clinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus. Circulation 2000, 102: e73-86. PMID: 10982554, DOI: 10.1161/01.cir.102.11.e73.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis Inducing AgentsAnimalsClinical Trials as TopicCoronary AngiographyCoronary VesselsEndothelial Growth FactorsFibroblast Growth Factor 2Genetic TherapyHeart DiseasesHumansLymphokinesMagnetic Resonance ImagingNeovascularization, PhysiologicPatient SelectionTomography, Emission-ComputedTomography, Emission-Computed, Single-PhotonVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsClinical trialsCoronary angiogenesisAdvanced ischemic heart diseaseAngiogenic growth factor therapySide effect profileIschemic heart diseaseGrowth factor therapyAppropriate patient populationAmerican Heart AssociationNew treatment strategiesTherapeutic end pointRoute of administrationBiology of angiogenesisNew blood supplyFactor therapyCoronary diseaseEffect profilePatient populationHeart AssociationHeart diseaseTreatment strategiesBlood supplyTherapeutic strategiesPreclinical investigationsTherapeutic angiogenesisEffect of Intracoronary Recombinant Human Vascular Endothelial Growth Factor on Myocardial Perfusion
Hendel R, Henry T, Rocha-Singh K, Isner J, Kereiakes D, Giordano F, Simons M, Bonow R. Effect of Intracoronary Recombinant Human Vascular Endothelial Growth Factor on Myocardial Perfusion. Circulation 2000, 101: 118-121. PMID: 10637195, DOI: 10.1161/01.cir.101.2.118.Peer-Reviewed Original ResearchMeSH KeywordsCardiotonic AgentsCoronary CirculationCoronary DiseaseCoronary VesselsDipyridamoleDobutamineDose-Response Relationship, DrugDouble-Blind MethodEndothelial Growth FactorsExercise TestHumansInjections, Intra-ArterialLymphokinesRecombinant ProteinsTomography, Emission-Computed, Single-PhotonVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVasodilator AgentsConceptsRecombinant human vascular endothelial growth factorSingle-photon emission CTVascular endothelial growth factorEndothelial growth factorMyocardial perfusionStress scoresHuman vascular endothelial growth factorGrowth factorPerfusion single-photon emission CTDose-dependent effectPhoton emission CTMyocardial perfusion single photon emission CTCoronary revascularizationRest scorePhase 1 dataAnimal modelsPatientsEmission CTLow dosesTherapeutic angiogenesisVisual findingsPerfusionStatistical significanceClinical applicationScores
1999
Therapeutic myocardial angiogenesis using percutaneous intrapericardial drug delivery
Laham R, Simons M, Hung D. Therapeutic myocardial angiogenesis using percutaneous intrapericardial drug delivery. Clinical Cardiology 1999, 22: 6-9. PMID: 9929761, PMCID: PMC6655779, DOI: 10.1002/clc.4960221305.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationCoronary VesselsDisease Models, AnimalEndothelial Growth FactorsFibroblast Growth Factor 1Fibroblast Growth Factor 2InjectionsLymphokinesMyocardial IschemiaNeovascularization, PhysiologicPericardiumReproducibility of ResultsSafetyVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
1998
Effects of coronary artery disease on expression and microvascular response to VEGF
Métais C, Li J, Li J, Simons M, Sellke F. Effects of coronary artery disease on expression and microvascular response to VEGF. American Journal Of Physiology 1998, 275: h1411-h1418. PMID: 9746492, DOI: 10.1152/ajpheart.1998.275.4.h1411.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateCell DivisionCoronary Artery BypassCoronary DiseaseEndothelial Growth FactorsEndothelium, VascularFemaleGene Expression RegulationGenisteinHeart AtriaHepatocyte Growth FactorHumansIn Vitro TechniquesKineticsLymphokinesMaleMicrocirculationMicroscopy, VideoMiddle AgedMuscle RelaxationMuscle, Smooth, VascularNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINitroarginineProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, MitogenReceptors, Vascular Endothelial Growth FactorRNA, MessengerTranscription, GeneticVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsVasodilationConceptsCoronary artery diseaseInducible nitric oxide synthaseConstitutive nitric oxide synthaseVascular endothelial growth factorHepatocyte growth factorExpression of VEGFNitric oxide synthaseArtery diseaseNG-nitroMicrovascular responsesOxide synthaseExpression of cNOSL-arginineGrowth factorCoronary microvascular responsesSubstance P responseExogenous vascular endothelial growth factorEndothelial growth factorFlk-1 receptorFlt-1 receptorMild hypercholesterolemiaTyrosine kinase receptorsTyrosine kinase inhibitor genisteinEndothelium dysfunctionVascular responsesComparison of VEGF Delivery Techniques on Collateral-Dependent Microvascular Reactivity
Sellke F, Tofukuji M, Laham R, Li J, Hariawala M, Bunting S, Simons M. Comparison of VEGF Delivery Techniques on Collateral-Dependent Microvascular Reactivity. Microvascular Research 1998, 55: 175-178. PMID: 9521892, DOI: 10.1006/mvre.1997.2066.Peer-Reviewed Original ResearchAdenosine DiphosphateAngina, UnstableAnimalsCollateral CirculationCoronary CirculationDrug Delivery SystemsEndothelial Growth FactorsFemaleLymphokinesMaleMicrocirculationMyocardial IschemiaNeovascularization, PhysiologicSwineVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVasodilationAngiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia
Lopez J, Edelman E, Stamler A, Hibberd M, Prasad P, Thomas K, Disalvo J, Caputo R, Carrozza J, Douglas P, Sellke F, Simons M. Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia. American Journal Of Physiology 1998, 274: h930-h936. PMID: 9530206, DOI: 10.1152/ajpheart.1998.274.3.h930.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationDisease Models, AnimalEndothelial Growth FactorsFibroblast Growth Factor 1Heart VentriclesLymphokinesMyocardial ContractionMyocardial IschemiaNeovascularization, PhysiologicRecombinant ProteinsSwineVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
1995
Magnetic resonance mapping demonstrates benefits of VEGF–induced myocardial angiogenesis
Pearlman J, Hibberd M, Chuang M, Harada K, Lopez J, Gladstone S, Friedman M, Sellke F, Simons M. Magnetic resonance mapping demonstrates benefits of VEGF–induced myocardial angiogenesis. Nature Medicine 1995, 1: 1085-1089. PMID: 7489368, DOI: 10.1038/nm1095-1085.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorMagnetic resonance imagingBlood supplyCoronary occlusive diseasePlacebo-controlled studyCollateral blood supplyBetter ejection fractionCoronary artery occlusionCause of deathCollateral vessel developmentEndothelial growth factorRegional wall thickeningArtery occlusionOcclusive diseaseEjection fractionCollateral vesselsCoronary arteryCollateral developmentIschemic zoneVEGF infusionMyocardial angiogenesisResonance imagingWall thickeningHeart attackPorcine modelβ-Adrenergic Modulation of the Collateral-Dependent Coronary Microcirculation
Sellke F, Wang S, Friedman M, Bin Dai H, Harada K, Lopez J, Simons M. β-Adrenergic Modulation of the Collateral-Dependent Coronary Microcirculation. Journal Of Surgical Research 1995, 59: 185-190. PMID: 7630126, DOI: 10.1006/jsre.1995.1152.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationCyclic AMPEndothelial Growth FactorsFemaleLymphokinesMaleMicrocirculationPerfusionReceptors, Adrenergic, betaSwineVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsVasodilationConceptsVascular endothelial growth factorCollateral-dependent LCx regionLCx regionCoronary microcirculationBlood flowProximal left circumflex coronary arteryLeft circumflex coronary arteryCollateral-dependent areaCollateral-dependent perfusionCoronary arterial microvesselsCoronary microvascular responsesLCX blood flowProximal (<b>d</b>) LCX arteryCircumflex coronary arteryCollateral-dependent myocardiumRapid atrial pacingEndothelial growth factorΒ-Adrenergic ModulationAdenylate cyclase activator forskolinRelaxations of microvesselsCyclase activator forskolinChronic treatmentLeft anteriorMicrovascular relaxationAtrial pacing