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 trialPharmacokinetics and Pharmacodynamics of Recombinant FGF‐2 in a Phase I Trial in Coronary Artery Disease
Bush M, Samara E, Whitehouse MJ, Yoshizawa C, Novicki D, Pike M, Laham R, Simons M, Chronos N. Pharmacokinetics and Pharmacodynamics of Recombinant FGF‐2 in a Phase I Trial in Coronary Artery Disease. The Journal Of Clinical Pharmacology 2001, 41: 378-385. PMID: 11304894, DOI: 10.1177/00912700122010230.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overArea Under CurveCoronary DiseaseEnzyme-Linked Immunosorbent AssayFemaleFibroblast Growth Factor 2Follow-Up StudiesHemodynamicsHeparinHumansInfusions, IntravenousMaleMaximum Tolerated DoseMetabolic Clearance RateMiddle AgedRecombinant ProteinsRegression AnalysisTime FactorsConceptsRecombinant FGF-2Coronary artery diseasePhase I trialFibroblast growth factor-2Artery diseaseI trialSystemic exposureSevere coronary artery diseaseTerminal elimination t1/2Peak plasma concentrationConcentration-time curveMultiple animal modelsDose-response relationshipAcute hemodynamicsGrowth factor 2Chronic ischemiaElimination t1/2Intravenous infusionSingle doseLinear pharmacokineticsDistribution t1/2Plasma concentrationsIntravenous administrationBiphasic eliminationSlow clearance
2000
Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease
Udelson J, Dilsizian V, Laham R, Chronos N, Vansant J, Blais M, Galt J, Pike M, Yoshizawa C, Simons M. Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease. Circulation 2000, 102: 1605-1610. PMID: 11015335, DOI: 10.1161/01.cir.102.14.1605.Peer-Reviewed Original ResearchConceptsAdvanced coronary diseaseCoronary diseaseRFGF-2Day 29Myocardial perfusionDay 180Day 57Chronic coronary artery diseaseTherapeutic angiogenesisRest perfusion scoreStress-induced ischemiaCoronary artery diseaseMyocardial perfusion abnormalitiesSingle photon emissionMechanical revascularizationNonstudy patientsArtery diseaseUncontrolled studiesDose groupPerfusion scanPerfusion abnormalitiesReversibility scoreIntravenous administrationPerfusion scoreFactor 2 (Nrf2) proteinBasic 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
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 deliveryCloning, Expression, andin VitroActivity of Human Endostatin
Dhanabal M, Volk R, Ramchandran R, Simons M, Sukhatme V. Cloning, Expression, andin VitroActivity of Human Endostatin. Biochemical And Biophysical Research Communications 1999, 258: 345-352. PMID: 10329390, DOI: 10.1006/bbrc.1999.0595.Peer-Reviewed Original Research
1998
Angiogenic 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
1996
Food for starving hearts
Simons M, Ware J. Food for starving hearts. Nature Medicine 1996, 2: 519-520. PMID: 8616705, DOI: 10.1038/nm0596-519.Peer-Reviewed Original Research