2014
Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium
Chen PY, Qin L, Tellides G, Simons M. Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium. Science Signaling 2014, 7: ra90. PMID: 25249657, DOI: 10.1126/scisignal.2005504.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell TransdifferentiationCoronary VesselsEndothelium, VascularExtracellular MatrixFibroblastsGraft RejectionHeart TransplantationHeterograftsHindlimbHuman Umbilical Vein Endothelial CellsHumansIschemiaMesodermMiceMice, Mutant StrainsMicroRNAsMuscle, Smooth, VascularNeointimaReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorSignal TransductionSmad2 ProteinTransforming Growth Factor betaTransplantation ChimeraConceptsFibroblast growth factor receptor 1Growth factor receptor 1Factor receptor 1Extracellular matrixSmooth muscle cellsMuscle cellsEndothelial cell-specific knockoutKey regulatorReceptor 1TGFβ signalingCell-specific knockoutDecreased abundanceMesenchymal transitionKey inhibitorVascular homeostasisGrowth factorDevelopment of EndMTRecurrence of stenosisTGFβGrowth of neointimaCellsNeointima formationEndMTVascular lumenSignalingThe 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
2012
FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of let-7 miRNA Expression
Chen PY, Qin L, Barnes C, Charisse K, Yi T, Zhang X, Ali R, Medina PP, Yu J, Slack FJ, Anderson DG, Kotelianski V, Wang F, Tellides G, Simons M. FGF Regulates TGF-β Signaling and Endothelial-to-Mesenchymal Transition via Control of let-7 miRNA Expression. Cell Reports 2012, 2: 1684-1696. PMID: 23200853, PMCID: PMC3534912, DOI: 10.1016/j.celrep.2012.10.021.Peer-Reviewed Original ResearchConceptsFibroblast growth factorEndo-MTMesenchymal transitionGrowth factorNormal endothelial functionBlood vessel functionTGF-β signalingEndothelial functionVascular pathologyEndothelial homeostasisNeointima formationVessel functionΒ ligandMiRNA levelsMiRNA expressionActivationExpressionUnexpected roleEndothelial 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
2008
Journeys in Coronary Angiogenesis
Paye J, Partovian C, Simons M. Journeys in Coronary Angiogenesis. 2008, 561-573. DOI: 10.1007/978-0-387-71518-6_47.Peer-Reviewed Original ResearchYoung animal modelsPotential therapeutic avenuesCoronary collateralsCoronary diseaseArterial occlusionCoronary vascular developmentClinical trialsCoronary angiogenesisIschemic tissueBlood flowExogenous growth factorsAnimal modelsTherapeutic neovascularizationTherapeutic avenuesGrowth factorVessel developmentVascular developmentBasic sciencePatientsBypassNeovascularizationDiseaseTrialsOcclusion
2007
Introductory Essay: Endothelial Cell Coupling
Simons M. Introductory Essay: Endothelial Cell Coupling. 2007, 627-631. DOI: 10.1017/cbo9780511546198.070.Peer-Reviewed Original ResearchSerine/threonine kinaseG protein-coupled receptorsEndothelial cellsTyrosine kinase receptorsAdhesion moleculesThreonine kinaseKinase receptorsEndothelial cell couplingExtracellular matrixSoluble ligandsTight junctionsGrowth factorCell couplingCellsEC interactionsCellular adhesion moleculesKinaseSyndecansReceptorsVessel wallIntegrinsMoleculesSolid phase environmentsBlood cellsAppropriate responseFibroblast Growth Factors
Murakami M, Elfenbein A, Simons M. Fibroblast Growth Factors. 2007, 291-303. DOI: 10.1017/cbo9780511546198.035.Peer-Reviewed Original ResearchFGF genesFibroblast growth factorGene duplicationGrowth factorBovine brainFGF receptor genesBasic isoelectric pointBALB/c 3T3 fibroblast cellsEarly vertebratesCaenorhabditis elegansDrosophila melanogasterFruit flyFGFR genesBasic fibroblast growth factorAcidic fibroblast growth factorGenesHeparin-Sepharose chromatographyReceptor geneProteinNomenclature CommitteeSepharose chromatographyFibroblast cellsBasic proteinMyelin basic proteinDuplicationEndothelial Activation and Neointimal Hyperplasia: A Double-Edged Sword
Khurana R, Simons M. Endothelial Activation and Neointimal Hyperplasia: A Double-Edged Sword. 2007, 75-84. DOI: 10.1007/1-4020-5955-8_4.Peer-Reviewed Original ResearchActivated endothelial cellsAngiogenic growth factorsNeointimal thickeningEndothelial cellsGrowth factorPercutaneous revascularization proceduresVascular smooth muscle cellsNumerous preclinical modelsVasa vasorum neovascularizationEndothelial cell activationVessel wall remodelingSmooth muscle cellsRole of VEGFPotent angiogenic growth factorRevascularization proceduresStent eraEndothelial activationInflammatory cellsNew capillary growthParacrine sourceVascular responsesNeointimal accumulationEndothelial repairEndovascular proceduresPreclinical modelsSynectin‐dependent suppression of basal Rac1 activity is reversed by a signaling pathway involving PKCalpha and RhoG
Elfenbein A, Simons M. Synectin‐dependent suppression of basal Rac1 activity is reversed by a signaling pathway involving PKCalpha and RhoG. The FASEB Journal 2007, 21: lb11-lb12. DOI: 10.1096/fasebj.21.6.lb11-d.Peer-Reviewed Original ResearchFibroblast growth factorEndothelial cellsHigh-affinity tyrosine kinase receptorsLow baseline levelsRac1 activitySerum-starved endothelial cellsHigh-affinity receptorTyrosine kinase receptorsBaseline levelsGrowth factorInhibitor-1Endothelial cell migrationHeparan sulfate proteoglycanDissociation inhibitor 1Kinase receptorsMigratory responseEarly eventsNovel roleSulfate proteoglycanCell migration
2006
Syndecan‐4 plays a key role in the phosphorylation of protein kinase B / Akt
Partovian C, Simons M. Syndecan‐4 plays a key role in the phosphorylation of protein kinase B / Akt. The FASEB Journal 2006, 20: a1080-a1080. DOI: 10.1096/fasebj.20.5.a1080-a.Peer-Reviewed Original ResearchPhosphoinositide-dependent kinase 1Syndecan-4Akt phosphorylationProtein kinase B/AktPhosphorylation of Thr308Hydrophobic motifActivation loopRaft fractionsEndothelial cellsKinase 1Akt activationPhosphorylationMammalian targetSyndecansThr308AktGrowth factorCentral roleRegulationCellsKey roleMajor roleRictorNumber of processesSer473
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 ResearchConceptsRecombinant 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 levels
2000
Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study
Laham R, Chronos N, Pike M, Leimbach M, Udelson J, Pearlman J, Pettigrew R, Whitehouse MJ, Yoshizawa C, Simons M. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study. Journal Of The American College Of Cardiology 2000, 36: 2132-2139. PMID: 11127452, DOI: 10.1016/s0735-1097(00)00988-8.Peer-Reviewed Original ResearchConceptsIntracoronary basic fibroblast growth factorOpen-label dose-escalation studyDose-escalation studyIschemic heart diseaseBasic fibroblast growth factorFibroblast growth factorHeart diseaseGrowth factorPhase I open-label dose-escalation studyFGF-2Non-Q-wave myocardial infarctionSevere ischemic heart diseaseSeattle Angina QuestionnaireTreadmill exercise testingQuality of lifeRegional wall thickeningMagnetic resonance imagingRFGF-2Angina QuestionnaireExercise toleranceRetinal examinationEscalation studyExercise testingIntracoronary administrationLaboratory parametersBasic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts
Hampton T, Amende I, Fong J, Laubach V, Li J, Metais C, Simons M. Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused mouse hearts. AJP Heart And Circulatory Physiology 2000, 279: h260-h268. PMID: 10899065, DOI: 10.1152/ajpheart.2000.279.1.h260.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCoronary VesselsEnzyme InhibitorsFemaleFibroblast Growth Factor 2HeartIn Vitro TechniquesLysineMaleMiceMice, Inbred C57BLMice, KnockoutMyocardial IschemiaMyocardial ReperfusionMyocardial StunningNG-Nitroarginine Methyl EsterNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsConceptsFGF-2Mouse heartsBasic FGFIschemia-reperfusion injuryExpression of NOS2Onset of ischemiaInducible NO synthaseBasic fibroblast growth factorNitric oxide productionNO-selective electrodeFibroblast growth factorLV dysfunctionIschemic contractureVentricular functionLV recoveryNO synthaseIntracellular calciumProtective effectTransgenic heartsOxide productionIschemiaGrowth factorReperfusionSelective inhibitorVehicle controlTherapeutic Angiogenesis
Simons M, Laham R, Post M, Sellke F. Therapeutic Angiogenesis. BioDrugs 2000, 14: 13-20. PMID: 18034552, DOI: 10.2165/00063030-200014010-00002.Peer-Reviewed Original ResearchGrowth factorTherapeutic angiogenesisAdvanced coronary diseaseAdverse effect profileInitial clinical dataRecent clinical experienceBasic fibroblast growth factorQuality of lifeAngiogenic growth factorsFibroblast growth factorCoronary diseaseEffect profileClinical dataPreclinical studiesAnimal modelsClinical experienceNew vasculatureClinical applicationPractical clinical applicationsAngiogenesisBFGFBasic biologyPatientsFactorsSymptomsEffect 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
Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery
Laham R, Sellke F, Edelman E, Pearlman J, Ware J, Brown D, Gold J, Simons M. Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery. Circulation 1999, 100: 1865-1871. PMID: 10545430, DOI: 10.1161/01.cir.100.18.1865.Peer-Reviewed Original ResearchMeSH KeywordsAlginatesCoronary Artery BypassCoronary VesselsDelayed-Action PreparationsDouble-Blind MethodDrug CarriersDrug CompoundingDrug ImplantsFemaleFibroblast Growth Factor 2Follow-Up StudiesGlucuronic AcidHeparinHexuronic AcidsHumansMaleMiddle AgedPatient SelectionPlacebosRecombinant ProteinsConceptsBasic fibroblast growth factorBFGF groupFibroblast growth factorTreatment-related adverse eventsQ-wave myocardial infarctionGrowth factorLocal perivascular deliverySerum bFGF levelsPlacebo-controlled studyCoronary bypass surgerySubset of patientsMode of therapyMagnetic resonance assessmentPromising treatment strategyNuclear perfusionOperative deathsRecurrent anginaStandard revascularizationNew blood vesselsPlacebo groupRepeat revascularizationAdverse eventsBypass surgeryControl patientsPerivascular deliveryPhosphatidylinositol-4,5-bisphosphate Mediates the Interaction of Syndecan-4 with Protein Kinase C †
Horowitz A, Murakami M, Gao Y, Simons M. Phosphatidylinositol-4,5-bisphosphate Mediates the Interaction of Syndecan-4 with Protein Kinase C †. Biochemistry 1999, 38: 15871-15877. PMID: 10625452, DOI: 10.1021/bi991363i.Peer-Reviewed Original ResearchConceptsCytoplasmic tailSyndecan-4Protein kinase CalphaProtein kinase CExtracellular matrix proteinsActivation of PKCalphaGrowth factorExtracellular signalsDelta isoenzymesTransmembrane proteoglycansKinase CMatrix proteinsPhosphatidylinositolPKCalphaActivation mechanismCooperative activationBisphosphateActivationProteoglycansRecent studiesTailPICalphaSignalingAffinityAngiogenesis in Cardiovascular Disease
Sellke F, Simons M. Angiogenesis in Cardiovascular Disease. Drugs 1999, 58: 391-396. PMID: 10493268, DOI: 10.2165/00003495-199958030-00001.Peer-Reviewed Original ResearchConceptsInoperable coronary artery diseaseTherapeutic angiogenesisChronic myocardial ischaemiaCoronary artery diseasePreliminary clinical trialsAngiogenic growth factorsMyocardial revascularisationArtery diseaseMyocardial ischaemiaTreatment optionsGrowth factor proteinClinical trialsCardiovascular diseaseMyocardial perfusionProtein administrationAnimal modelsAngiogenic factorsObjective evidenceGrowth factorAngiogenesisPatientsDiseaseAdministrationGene therapyOptimal candidatesTherapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies.
Laham R, Garcia L, Baim D, Post M, Simons M. Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies. Current Interventional Cardiology Reports 1999, 1: 228-233. PMID: 11096629.Peer-Reviewed Original ResearchVascular endothelial growth factorBasic fibroblast growth factorEndothelial growth factorGrowth factorFibroblast growth factorDouble-blind placebo-controlled trialIntravenous deliveryTherapeutic angiogenesisStandard revascularization proceduresPlacebo-controlled trialLarger patient populationChronic myocardial ischemiaDelivery strategiesPerivascular deliveryRevascularization proceduresPatient populationAtrial injectionIntrapericardial administrationTreatment modalitiesMyocardial ischemiaSustained administrationTreatment strategiesClinical studiesOutcome measuresIntramyocardial administration