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 lumenSignaling
2001
Expression 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 levelsSerotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition
Métais C, Bianchi C, Li J, Li J, Simons M, Sellke F. Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. Basic Research In Cardiology 2001, 96: 59-67. PMID: 11215533, DOI: 10.1007/s003950170078.Peer-Reviewed Original ResearchMeSH KeywordsAgedCoronary VesselsCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase InhibitorsFemaleHeart AtriaHumansIsoenzymesMaleMembrane ProteinsMicrocirculationMiddle AgedMyocardial IschemiaMyocardiumNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINitroprussideProstaglandin-Endoperoxide SynthasesSerotoninSubstance PVasoconstrictionConceptsAcute myocardial ischemiaMyocardial ischemiaContractile responseCoronary arteriolesPotent contractile responseAcute coronary syndromeCOX-2 expressionCOX-2 inhibitionCOX-2 mRNAMicrovascular contractionSNP relaxationCoronary spasmCoronary syndromeL-NNACardiac surgeryAtherosclerotic patientsSubstance PNOS-2Prostaglandin releaseCOX-1IschemiaAtrial tissueSodium nitroprussideNOS-3Prostacyclin synthase
2000
Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia
Sato K, Laham R, Pearlman J, Novicki D, Sellke F, Simons M, Post M. Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. The Annals Of Thoracic Surgery 2000, 70: 2113-2118. PMID: 11156130, DOI: 10.1016/s0003-4975(00)02018-x.Peer-Reviewed Original ResearchConceptsChronic myocardial ischemiaRegional blood flowIschemic myocardiumFGF-2Myocardial ischemiaBlood flowPig modelML/min/Perfusion magnetic resonance imagingSingle intravenous infusionGrowth factor administrationRegional wall motionMagnetic resonance imagingAngiographic collateralsIntracoronary treatmentEjection fractionIntracoronary infusionIntravenous infusionIschemic areaFactor administrationMyocardial functionColored microspheresMyocardial perfusionResonance imagingTherapeutic angiogenesisClinical 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 angiogenesisBasic 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 controlEffect 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 applicationScoresPR39, a peptide regulator of angiogenesis
Li J, Post M, Volk R, Gao Y, Li M, Metais C, Sato K, Tsai J, Aird W, Rosenberg R, Hampton T, Li J, Sellke F, Carmeliet P, Simons M. PR39, a peptide regulator of angiogenesis. Nature Medicine 2000, 6: 49-55. PMID: 10613823, DOI: 10.1038/71527.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimicrobial Cationic PeptidesAortaCapillariesCattleCell HypoxiaCells, CulturedCoronary VesselsCysteine EndopeptidasesDNA-Binding ProteinsEndothelium, VascularHeartHumansHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitIn Vitro TechniquesMacrophagesMiceMice, Inbred C57BLMice, TransgenicMultienzyme ComplexesMyocardial InfarctionMyocardial IschemiaNeovascularization, PhysiologicNuclear ProteinsPeptidesProteasome Endopeptidase ComplexRecombinant ProteinsSwineTranscription FactorsUbiquitinsUmbilical VeinsVon Willebrand FactorConceptsHypoxia-inducible factor-1α (HIF-1α) degradationMacrophage-derived peptideHypoxia-inducible factor-1α (HIF-1α) proteinCoronary flow studiesInflammation-induced angiogenesisInduction of angiogenesisMyocardial vasculatureTissue injuryPotent inductorFunctional blood vesselsBlood vesselsVascular structuresAngiogenesisSelective inhibitionPR39
1999
Serotonin-Induced Coronary Contraction Increases After Blood Cardioplegia-Reperfusion
Métais C, Li J, Li J, Simons M, Sellke F. Serotonin-Induced Coronary Contraction Increases After Blood Cardioplegia-Reperfusion. Circulation 1999, 100: ii-328-ii-334. PMID: 10567324, DOI: 10.1161/01.cir.100.suppl_2.ii-328.Peer-Reviewed Original ResearchConceptsAtrial arteriolesBlood cardioplegiaVasomotor regulationSubstance PCOX-2Constitutive endothelial nitric oxide synthaseNitric oxideEndothelial nitric oxide synthaseCoronary microvascular regulationHyperkalemic blood cardioplegiaPotent contractile responseEndothelium-independent relaxationCoronary artery surgeryCoronary bypass surgeryEndothelium-dependent relaxationCoronary artery diseaseNitric oxide synthaseReverse transcriptase-polymerase chain reactionRelease of prostaglandinsBrief reperfusionCoronary contractionArtery surgeryCoronary spasmBypass surgeryContractile responseLocal 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 deliveryAngiogenesis 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 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
Anti-C5a monoclonal antibody reduces cardiopulmonary bypass and cardioplegia-induced coronary endothelial dysfunction
Tofukuji M, Stahl G, Agah A, Metais C, Simons M, Sellke F, This study was supported by National Institutes of Health grants HL46716 H. Anti-C5a monoclonal antibody reduces cardiopulmonary bypass and cardioplegia-induced coronary endothelial dysfunction. Journal Of Thoracic And Cardiovascular Surgery 1998, 116: 1060-1068. PMID: 9832699, DOI: 10.1016/s0022-5223(98)70059-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCardiopulmonary BypassChemotaxis, LeukocyteComplement C5aCoronary VesselsEndothelium, VascularFemaleHeart Arrest, InducedHemodynamicsMaleMiceMice, Inbred BALB CMyocardial Reperfusion InjuryNeutrophilsNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPeroxidaseSwineConceptsEndothelium-dependent relaxationSaline solution groupCardiopulmonary bypassMonoclonal antibodiesCardioplegic reperfusionSolution groupImpaired endothelium-dependent relaxationAnti-C5a monoclonal antibodyCoronary endothelial dysfunctionPolymorphonuclear leukocyte infiltrationLeft ventricular pressureSaline solution vehiclePercent segmental shorteningMonoclonal antibody groupC5a inhibitionEndothelial dysfunctionMyeloperoxidase activityCoronary arteriolesLeukocyte infiltrationSegmental shorteningCoronary arteryHyperkalemic cardioplegiaFunctional preservationVentricular pressureVascular studiesTherapeutic Angiogenesis With Basic Fibroblast Growth Factor: Technique and Early Results
Sellke F, Laham R, Edelman E, Pearlman J, Simons M. Therapeutic Angiogenesis With Basic Fibroblast Growth Factor: Technique and Early Results. The Annals Of Thoracic Surgery 1998, 65: 1540-1544. PMID: 9647055, DOI: 10.1016/s0003-4975(98)00340-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlginatesAngina PectorisCollateral CirculationCoronary Artery BypassCoronary Artery DiseaseCoronary CirculationCoronary VesselsCreatinineDelayed-Action PreparationsDrug CarriersFeasibility StudiesFemaleFibroblast Growth Factor 2Follow-Up StudiesGlucuronic AcidHeparinHexuronic AcidsHumansMaleMiddle AgedMyocardial ContractionMyocardial InfarctionNeovascularization, PhysiologicPericardiumSafetyStroke VolumeSurvival RateConceptsBasic fibroblast growth factorCoronary artery bypassFibroblast growth factorArtery bypassGrowth factorTherapeutic angiogenesisConventional coronary artery bypassBasic fibroblast growth factor (bFGF) administrationSlow-release devicesStress perfusion scansPerioperative myocardial infarctionSerum creatinine levelsDifficult clinical problemFixed perfusion defectsLong-term resultsMyocardial contractile functionGrowth factor administrationOperative mortalityPatent arteriesMyocardial revascularizationCreatinine levelsEjection fractionClinical efficacyHepatic toxicityPerfusion scan
1997
Angiogenesis in ischemic heart disease
Ware J, Simons M. Angiogenesis in ischemic heart disease. Nature Medicine 1997, 3: 158-164. PMID: 9018233, DOI: 10.1038/nm0297-158.Peer-Reviewed Original Research
1996
Direct Vasomotor Effects of Isoflurane in Subepicardial Resistance Vessels from Collateral-dependent and Normal Coronary Circulation of Pigs
Park K, Lowenstein E, Dai H, Lopez J, Stamler A, Simons M, Sellke F. Direct Vasomotor Effects of Isoflurane in Subepicardial Resistance Vessels from Collateral-dependent and Normal Coronary Circulation of Pigs. Anesthesiology 1996, 85: 584-591.. PMID: 8853089, DOI: 10.1097/00000542-199609000-00018.Peer-Reviewed Original ResearchConceptsDirect vasomotor effectResistance vesselsVasomotor effectsNormal vesselsCoronary arteryEndothelin-1Sodium nitroprussideEndothelium-independent dilator sodium nitroprussideNormal coronary circulationResistance coronary arteriesCoronary resistance vesselsChronic coronary occlusionConcentration-dependent constrictionThromboxane analog U46619 1 microMLeft circumflex arteryRapid atrial pacingMyocardial blood flowEndothelial dysfunctionVasoconstrictive effectAtrial pacingCircumflex arteryCoronary occlusionConstrictive effectOccluder placementCoronary circulation
1993
Relation between Activated Smooth-Muscle Cells in Coronary-Artery Lesions and Restenosis after Atherectomy
Simons M, Leclerc G, Safian R, Isner J, Weir L, Baim D. Relation between Activated Smooth-Muscle Cells in Coronary-Artery Lesions and Restenosis after Atherectomy. New England Journal Of Medicine 1993, 328: 608-613. PMID: 8429852, DOI: 10.1056/nejm199303043280903.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsMyosin heavy chainNonmuscle myosin heavy chainRecurrent luminal narrowingCoronary artery lesionsExercise thallium scintigraphyVascular smooth muscle cellsCoronary atherosclerotic plaquesPresence of restenosisHigh-power fieldGroup of lesionsNegative resultsAngiographic followCoronary atherectomyCoronary angioplastyThallium scintigraphyCoronary lesionsLuminal narrowingNeointimal proliferationSubsequent restenosisLate lossLuminal diameterHeavy chainHigh riskAtherectomy