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
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
2013
The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis
Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, Prahst C, Zhang J, Wang Y, Davis G, Toomre D, Ruhrberg C, Simons M. The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis. Developmental Cell 2013, 25: 156-168. PMID: 23639442, PMCID: PMC3774154, DOI: 10.1016/j.devcel.2013.03.019.Peer-Reviewed Original ResearchAnimalsArteriesCells, CulturedCytoplasmEndocytosisEndosomesEndothelium, VascularMAP Kinase Signaling SystemMiceMorphogenesisNeovascularization, PathologicNeuropilin-1PhosphorylationSignal TransductionTransferrinVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vesicular Transport Proteins
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 moleculesEfficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia
Sato K, Wu T, Laham R, Johnson R, Douglas P, Li J, Sellke F, Bunting S, Simons M, Post M. Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. Journal Of The American College Of Cardiology 2001, 37: 616-623. PMID: 11216988, DOI: 10.1016/s0735-1097(00)01144-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCoronary CirculationDose-Response Relationship, DrugEndothelial Growth FactorsEndothelium, VascularInfusions, Intra-ArterialInfusions, IntravenousLymphokinesMaleMicrocirculationMyocardial ContractionMyocardial IschemiaSwineVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsChronic myocardial ischemiaMyocardial ischemiaL-NAMEIntracoronary groupBlood flowNitro-L-arginine methyl ester hydrochlorideNitric oxide synthase inhibitionEndothelial growth factor treatmentLeft circumflex coronary arteryDose-limiting hypotensionOxide synthase inhibitionCircumflex coronary arteryVascular endothelial growth factor treatmentMyocardial blood flowRegional myocardial functionGrowth factor treatmentVEGF-induced angiogenesisIntravenous groupConcomitant administrationMicrovascular functionIntracoronary infusionCollateral indexDifferent regimensCoronary arteryIntravenous infusion
2000
Synectin, syndecan‐4 cytoplasmic domain binding PDZ protein, inhibits cell migration
Gao Y, Li M, Chen W, Simons M. Synectin, syndecan‐4 cytoplasmic domain binding PDZ protein, inhibits cell migration. Journal Of Cellular Physiology 2000, 184: 373-379. PMID: 10911369, DOI: 10.1002/1097-4652(200009)184:3<373::aid-jcp12>3.0.co;2-i.Peer-Reviewed Original ResearchConceptsSyndecan-4Cytoplasmic domainSyndecan-4 cytoplasmic domainTwo-hybrid libraryDomain-mediated interactionsNovel binding partnerInhibits cell migrationGene familyPDZ proteinsBinding partnerDependent regulationSynectinImportant regulatorCell adhesionCell migrationCell growthGrowth rateGIPCMigrationRegulatorDomainProteinTransportersOverexpressionNeuropilinsPR39, 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
Attenuation of Endothelium-Dependent Dilation of Pig Pulmonary Arterioles After Cardiopulmonary Bypass Is Prevented by Monoclonal Antibody to Complement C5a
Park K, Tofukuji M, Metais C, Comunale M, Dai H, Simons M, Stahl G, Agah A, Sellke F. Attenuation of Endothelium-Dependent Dilation of Pig Pulmonary Arterioles After Cardiopulmonary Bypass Is Prevented by Monoclonal Antibody to Complement C5a. Anesthesia & Analgesia 1999, 89: 42-48.. DOI: 10.1213/00000539-199907000-00008.Peer-Reviewed Original ResearchConceptsNitric oxide synthasePulmonary endothelial dysfunctionCardiopulmonary bypassEndothelial dysfunctionMonoclonal antibodiesPulmonary arteriolesComplement C5aPrevious administrationConstitutive nitric oxide synthaseAnti-C5a monoclonal antibodyEndothelium-dependent dilatorsEndothelium-dependent dilationTissue myeloperoxidase activityNormothermic cardiopulmonary bypassReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionNeutrophil sequestrationMyeloperoxidase activityMPO activityPolymerase chain reactionSubstance POxide synthaseSodium nitroprussideComplement activationRelaxation responseAttenuation of endothelium-dependent dilation of pig pulmonary arterioles after cardiopulmonary bypass is prevented by monoclonal antibody to complement C5a.
Park K, Tofukuji M, Metais C, Comunale M, Dai H, Simons M, Stahl G, Agah A, Sellke F. Attenuation of endothelium-dependent dilation of pig pulmonary arterioles after cardiopulmonary bypass is prevented by monoclonal antibody to complement C5a. Anesthesia & Analgesia 1999, 89: 42-8. PMID: 10389776, DOI: 10.1097/00000539-199907000-00008.Peer-Reviewed Original ResearchCloning, 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 ResearchEffect of sialyl Lewisx oligosaccharide on myocardial and cerebral injury in the pig
Tofukuji M, Metais C, Collard C, Morse D, Stahl G, Nelson D, Li J, Simons M, Sellke F. Effect of sialyl Lewisx oligosaccharide on myocardial and cerebral injury in the pig. The Annals Of Thoracic Surgery 1999, 67: 112-119. PMID: 10086534, DOI: 10.1016/s0003-4975(98)01130-8.Peer-Reviewed Original ResearchConceptsArtery blood flowCardiopulmonary bypassMyeloperoxidase activityBrain arteriolesNeutrophil infiltrationOrgan perfusionBlood flowInducible isoformInternal carotid artery blood flowEndothelium-dependent relaxation responsesCoronary artery blood flowCarotid artery blood flowLeft ventricular systolic pressureNitric oxide synthase mRNAAdministration of CYBeneficial acute effectsCerebral vascular resistanceEndothelium-independent relaxationEndothelium-dependent relaxationVentricular systolic pressureCoronary artery occlusionMyocardial contractile functionNormothermic cardiopulmonary bypassLeft ventricular pressureNitric oxide synthase
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 studiesEffects of coronary artery disease on expression and microvascular response to VEGF
Métais C, Li J, Li J, Simons M, Sellke F. Effects of coronary artery disease on expression and microvascular response to VEGF. American Journal Of Physiology 1998, 275: h1411-h1418. PMID: 9746492, DOI: 10.1152/ajpheart.1998.275.4.h1411.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateCell DivisionCoronary Artery BypassCoronary DiseaseEndothelial Growth FactorsEndothelium, VascularFemaleGene Expression RegulationGenisteinHeart AtriaHepatocyte Growth FactorHumansIn Vitro TechniquesKineticsLymphokinesMaleMicrocirculationMicroscopy, VideoMiddle AgedMuscle RelaxationMuscle, Smooth, VascularNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINitroarginineProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, MitogenReceptors, Vascular Endothelial Growth FactorRNA, MessengerTranscription, GeneticVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth FactorsVasodilationConceptsCoronary artery diseaseInducible nitric oxide synthaseConstitutive nitric oxide synthaseVascular endothelial growth factorHepatocyte growth factorExpression of VEGFNitric oxide synthaseArtery diseaseNG-nitroMicrovascular responsesOxide synthaseExpression of cNOSL-arginineGrowth factorCoronary microvascular responsesSubstance P responseExogenous vascular endothelial growth factorEndothelial growth factorFlk-1 receptorFlt-1 receptorMild hypercholesterolemiaTyrosine kinase receptorsTyrosine kinase inhibitor genisteinEndothelium dysfunctionVascular responses
1997
Enhancement of Migration by Protein Kinase Cα and Inhibition of Proliferation and Cell Cycle Progression by Protein Kinase Cδ in Capillary Endothelial Cells*
Harrington E, Löffler J, Nelson P, Kent K, Simons M, Ware J. Enhancement of Migration by Protein Kinase Cα and Inhibition of Proliferation and Cell Cycle Progression by Protein Kinase Cδ in Capillary Endothelial Cells*. Journal Of Biological Chemistry 1997, 272: 7390-7397. PMID: 9054439, DOI: 10.1074/jbc.272.11.7390.Peer-Reviewed Original Research
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 reactivity