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 formsEndothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension
Zhou X, Jiang Y, Wang Y, Fan L, Zhu Y, Chen Y, Wang Y, Zhu Y, Wang H, Pan Z, Li Z, Zhu X, Ren R, Ge Z, Lai D, Lai E, Chen T, Wang K, Liang P, Qin L, Liu C, Qiu C, Simons M, Yu L. Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension. Circulation Research 2023, 133: 508-531. PMID: 37589160, DOI: 10.1161/circresaha.122.321200.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionHypoxic pulmonary hypertensionPulmonary endothelial functionHuman pulmonary artery endothelial cellsPulmonary artery endothelial cellsPulmonary endotheliumArtery endothelial cellsEndothelial functionEndothelial cellsEndothelial mitochondriaSugen/hypoxia rat modelClinical specimensPulmonary endothelial dysfunctionHypoxia rat modelPulmonary arterial systemHypoxic stressVascular remodeling diseasePrevious clinical researchHuman embryonic stem cell-derived endothelial cellsMitochondrial oxygen consumption rateIntrinsic pathogenesisEndothelial dysfunctionExtracellular acidification rateHypoxic ratsPoor prognosisAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4
2022
Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model.
Qin L, Jiang B, Zsebo K, Duckers H, Simons M, Chen P. Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model. Journal Of Visualized Experiments 2022 PMID: 36440832, DOI: 10.3791/63839.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionInvasive hemodynamic assessmentHemodynamic assessmentPAH modelProgressive life-threatening diseaseGroup 3 diseaseRight ventricle catheterizationSmall pulmonary arteriolesIntravenous bolus dosingNew experimental therapiesLife-threatening diseaseAdministration of compoundsMouse jugular veinHuman clinical manifestationsArterial hypertensionHypertension modelPulmonary arteriolesClinical manifestationsBolus dosingExperimental therapiesIntravenous administrationJugular veinPAH researchMultiple injectionsTime course
2019
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
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
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
2013
Endothelial ERK signaling controls lymphatic fate specification
Deng Y, Atri D, Eichmann A, Simons M. Endothelial ERK signaling controls lymphatic fate specification. Journal Of Clinical Investigation 2013, 123: 1202-1215. PMID: 23391722, PMCID: PMC3582116, DOI: 10.1172/jci63034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaBody PatterningButadienesCells, CulturedEndothelium, LymphaticExtracellular Signal-Regulated MAP KinasesFemaleGene ExpressionGene Expression Regulation, DevelopmentalHomeodomain ProteinsHuman Umbilical Vein Endothelial CellsHumansLymphangiectasisLymphangiogenesisMaleMAP Kinase Signaling SystemMiceMice, TransgenicMutation, MissenseNitrilesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-rafSOXF Transcription FactorsTumor Suppressor ProteinsUp-RegulationVascular Endothelial Growth Factor Receptor-3ConceptsFate specificationERK activationSOX18 expressionEndothelial cellsLymphatic endothelial cellsInhibition of ERKLymphatic fateDifferentiation programNoonan syndromeLymphatic phenotypeInducible expressionRAF1 geneMolecular eventsFunction mutationsProx1 expressionVenous endothelial cellsCardinal veinERKExpressionLymphatic vesselsKey roleRelated diseasesSOX18ActivationExcessive production
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 factorSyndecan 4 Regulates FGFR1 Signaling in Endothelial Cells by Directing Macropinocytosis
Elfenbein A, Lanahan A, Zhou TX, Yamasaki A, Tkachenko E, Matsuda M, Simons M. Syndecan 4 Regulates FGFR1 Signaling in Endothelial Cells by Directing Macropinocytosis. Science Signaling 2012, 5: ra36. PMID: 22569333, PMCID: PMC3827948, DOI: 10.1126/scisignal.2002495.Peer-Reviewed Original ResearchConceptsFGF receptor 1Mitogen-activated protein kinaseFibroblast growth factor-2MAPK signalingSyndecan-4Inhibition of Rab5Receptor tyrosine kinasesEndothelial cell migrationHeparan sulfate proteoglycanSignal transductionProtein kinaseFGF2 stimulationEndothelial cellsMAPK activationTyrosine kinaseGrowth factor 2Genetic knockoutCell migrationReceptor complexMacropinocytosisClasses of receptorsSignalingRab5Factor 2Sulfate proteoglycan
2001
PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation
Bao J, Sato K, Li M, Gao Y, Abid R, Aird W, Simons M, Post M. PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation. AJP Heart And Circulatory Physiology 2001, 281: h2612-h2618. PMID: 11709430, DOI: 10.1152/ajpheart.2001.281.6.h2612.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesCells, CulturedCysteine EndopeptidasesDNA-Binding ProteinsEndothelium, VascularHumansI-kappa B ProteinsIntercellular Adhesion Molecule-1MaleMultienzyme ComplexesMyocardial Reperfusion InjuryMyocardiumNADPH OxidasesNeutrophilsNF-KappaB Inhibitor alphaPeptide FragmentsPeroxidasePhosphoproteinsProteasome Endopeptidase ComplexRatsRats, Sprague-DawleyReactive Oxygen SpeciesUmbilical VeinsVascular Cell Adhesion Molecule-1Ventricular Function, LeftConceptsIschemia-reperfusion injuryB alpha degradationAdhesion molecule-1PR-11Alpha degradationNeutrophil infiltrationMyeloperoxidase activityInfarct sizeMolecule-1Vascular cell adhesion molecule-1Myocardial ischemia-reperfusion injuryIntercellular adhesion molecule-1Cell adhesion molecule-1Ventricular systolic pressureTime of reperfusionIschemia-reperfusion modelMin of ischemiaPR-39Controls 24 hBlood pressureSystolic pressureCardiac functionIntramyocardial injectionIκBα degradationAdhesion moleculesIntracoronary 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 trialAn anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study)
Rusnak J, Kopecky S, Clements I, Gibbons R, Holland A, Peterman H, Martin J, Saoud J, Feldman R, Breisblatt W, Simons M, Gessler C, Yu A, Investigators F. An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study). The American Journal Of Cardiology 2001, 88: 482-487. PMID: 11524054, DOI: 10.1016/s0002-9149(01)01723-4.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngioplasty, Balloon, CoronaryAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedChi-Square DistributionCombined Modality TherapyCoronary AngiographyDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleElectrocardiographyFemaleFollow-Up StudiesHumansInfusions, IntravenousMaleMiddle AgedMyocardial InfarctionNeuroprotective AgentsPilot ProjectsProbabilitySensitivity and SpecificitySeverity of Illness IndexStatistics, NonparametricSurvival RateTomography, Emission-Computed, Single-PhotonTreatment OutcomeConceptsPercutaneous transluminal coronary angioplastyAcute myocardial infarctionIntercellular adhesion molecule-1Hu23F2GTransluminal coronary angioplastyCD11/CD18Monoclonal antibodiesCoronary angioplastyMyocardial infarctionCD11/CD18 monoclonal antibodyMyocardial single photon emissionInitial clinical safetySubsequent cardiac interventionsST-segment elevationHumanized monoclonal antibodyActivation of neutrophilsAdhesion molecule-1CD18 monoclonal antibodySignificant differencesG treatment groupsNear-baseline valuesSingle photon emissionAdverse eventsCoronary reperfusionInflammatory mediatorsTherapeutic 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 ResearchExpression 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 levelsPharmacokinetics 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 clearanceTherapeutic 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 ResearchConceptsPromising 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