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
Endothelial Cell–Dependent Regulation of Arteriogenesis
Moraes F, Paye J, Mac 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
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 trialTherapeutic coronary angiogenesis: a fronte praecipitium a tergo lupi? *
Simons M. Therapeutic coronary angiogenesis: a fronte praecipitium a tergo lupi? *. AJP Heart And Circulatory Physiology 2001, 280: h1923-h1927. PMID: 11299191, DOI: 10.1152/ajpheart.2001.280.5.h1923.Peer-Reviewed Original ResearchAnimalsCoronary CirculationCoronary DiseaseHumansMyocardial RevascularizationNeovascularization, PhysiologicTherapeutic 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 AGENE TRANSFER FOR ANGIOGENESIS IN CORONARY ARTERY DISEASE
Laham R, Simons M, Sellke F. GENE TRANSFER FOR ANGIOGENESIS IN CORONARY ARTERY DISEASE. Annual Review Of Medicine 2001, 52: 485-502. PMID: 11160791, DOI: 10.1146/annurev.med.52.1.485.Peer-Reviewed Original ResearchMeSH KeywordsCoronary DiseaseEthics, MedicalForecastingGene Transfer TechniquesGenetic VectorsHumansNeovascularization, PhysiologicPatient AdvocacyResearch DesignTreatment OutcomeConceptsPromising novel therapeutic strategyAvailable preclinical dataStandard revascularization strategyPeripheral vascular diseaseCoronary artery diseasePreliminary clinical experienceNovel therapeutic strategiesCell-based vectorsRevascularization strategyArtery diseasePreclinical dataVascular diseaseClinical trialsIschemic heartBlood flowTherapeutic strategiesClinical experienceTherapeutic angiogenesisAngiogenesisDelivery modalitiesGene transfer studiesDiseaseGene transfer vectorsPreliminary naturePatients
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 angiogenesisTherapeutic 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) proteinClinical 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 angiogenesisMolecular multitasking: statins lead to more arteries, less plaque
Simons M. Molecular multitasking: statins lead to more arteries, less plaque. Nature Medicine 2000, 6: 965-966. PMID: 10973306, DOI: 10.1038/79646.Peer-Reviewed Original ResearchAnticholesteremic AgentsArteriosclerosisEnzyme ActivationHydroxymethylglutaryl-CoA Reductase InhibitorsNeovascularization, PhysiologicNitric Oxide SynthaseNitric Oxide Synthase Type IIIProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionSimvastatinPR39, 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
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
Therapeutic 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 scanComparison 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
1996
Angiogenesis induced by acidic fibroblast growth factor as an alternative method of revascularization for chronic myocardial ischemia
Sellke F, Li J, Stamler A, Lopez J, Thomas K, Simons M. Angiogenesis induced by acidic fibroblast growth factor as an alternative method of revascularization for chronic myocardial ischemia. Surgery 1996, 120: 182-188. PMID: 8751581, DOI: 10.1016/s0039-6060(96)80286-8.Peer-Reviewed Original ResearchConceptsCollateral-dependent LCx regionAcidic fibroblast growth factorFibroblast growth factorLCx regionBlood flowSodium nitroprussideProximal left circumflex coronary arterySevere coronary artery diseaseLeft circumflex coronary arteryGrowth factorCoronary arterial microvesselsCoronary microvascular reactivityProximal (<b>d</b>) LCX arteryEndothelium-dependent mechanismEndothelium-dependent relaxationCircumflex coronary arteryCollateral-dependent myocardiumCoronary artery diseaseTreatment of patientsGuanylate cyclase activators sodium nitroprussideChronic myocardial ischemiaAdenylate cyclase activator forskolinPeriadventitial administrationCyclase activator forskolinMicrovascular reactivityFood 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 ResearchAnimalsFibroblast Growth Factor 5Fibroblast Growth FactorsGenetic TherapyHumansMyocardial IschemiaNeovascularization, PhysiologicRecombinant ProteinsSwine