Featured Publications
Syndecan-2 selectively regulates VEGF-induced vascular permeability
Corti F, Ristori E, Rivera-Molina F, Toomre D, Zhang J, Mihailovic J, Zhuang ZW, Simons M. Syndecan-2 selectively regulates VEGF-induced vascular permeability. Nature Cardiovascular Research 2022, 1: 518-528. PMID: 36212522, PMCID: PMC9544384, DOI: 10.1038/s44161-022-00064-2.Peer-Reviewed Original ResearchN-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization
Corti F, Wang Y, Rhodes JM, Atri D, Archer-Hartmann S, Zhang J, Zhuang ZW, Chen D, Wang T, Wang Z, Azadi P, Simons M. N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization. Nature Communications 2019, 10: 1562. PMID: 30952866, PMCID: PMC6450910, DOI: 10.1038/s41467-019-09605-z.Peer-Reviewed Original ResearchSyndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development
Wang Y, Baeyens N, Corti F, Tanaka K, Fang J, Zhang J, Jin Y, Coon B, Hirschi K, Schwartz M, Simons M. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Journal Of Cell Science 2016, 129: e1.1-e1.1. DOI: 10.1242/jcs.200089.Peer-Reviewed Original ResearchModulation of VEGF receptor 2 signaling by protein phosphatases
Corti F, Simons M. Modulation of VEGF receptor 2 signaling by protein phosphatases. Pharmacological Research 2016, 115: 107-123. PMID: 27888154, PMCID: PMC5205541, DOI: 10.1016/j.phrs.2016.11.022.Peer-Reviewed Original ResearchConceptsProtein phosphatasePhosphorylation of serineVascular endothelial growth factor receptor 2 signalingSignal transduction cascadePrecise biological roleSpecific signaling pathwaysKinase biologyEukaryotic cellsSignal terminatorRegulatory subunitPositive regulatorTransduction cascadePhosphorylation stateBiological roleContext of cancerParticular proteinDifferent proteinsGenome sequencingSignaling pathwaysVEGF receptor 2Receptor 2 signalingVEGF signalsProteinPhosphataseGenetic modelsSyndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 17308-17313. PMID: 25404299, PMCID: PMC4260558, DOI: 10.1073/pnas.1413725111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlotting, WesternCells, CulturedEndothelial CellsFemaleHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNF-kappa BReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionStress, MechanicalSyndecan-4Vascular Endothelial Growth Factor Receptor-2ConceptsHuman umbilical vein endothelial cellsNF-κBProinflammatory NF-κBAtherosclerotic plaque burdenKruppel-like factor 2Umbilical vein endothelial cellsVEGF receptor 2Appearance of plaquesVein endothelial cellsHypercholesterolemic micePlaque burdenAntiinflammatory pathwayThoracic aortaReceptor 2Endothelial cellsEndothelial alignmentFlow correlatesCausal roleAtherosclerosisFactor 2MiceCyclic stretchLocalization correlatesActivationSyndecan-4The Syndecan-4/Protein Kinase Cα Pathway Mediates Prostaglandin E2-induced Extracellular Regulated Kinase (ERK) Activation in Endothelial Cells and Angiogenesis in Vivo *
Corti F, Finetti F, Ziche M, Simons M. The Syndecan-4/Protein Kinase Cα Pathway Mediates Prostaglandin E2-induced Extracellular Regulated Kinase (ERK) Activation in Endothelial Cells and Angiogenesis in Vivo *. Journal Of Biological Chemistry 2013, 288: 12712-12721. PMID: 23525101, PMCID: PMC3642317, DOI: 10.1074/jbc.m113.452383.Peer-Reviewed Original ResearchConceptsERK activationExtracellular-regulated kinase activationProteoglycan syndecan-4Protein kinase CαEndothelial cell migrationKinase activationEndothelial cellsSyndecan-4Full rescueCord formationCell migrationActivation of angiogenesisMatrigel assaysTransductionAngiogenic responseAngiogenesisActivationTumor growthImportant roleCellsMutantsMain mediatorVivoSDC4PKCα
2022
Author Correction: Syndecan-2 selectively regulates VEGF-induced vascular permeability
Corti F, Ristori E, Rivera-Molina F, Toomre D, Zhang J, Mihailovic J, Zhuang Z, Simons M. Author Correction: Syndecan-2 selectively regulates VEGF-induced vascular permeability. Nature Cardiovascular Research 2022, 1: 592-592. PMID: 39195875, DOI: 10.1038/s44161-022-00092-y.Peer-Reviewed Original ResearchEditorial: Proteoglycans in the Tumor Microenvironment.
Brunetti J, Viola M, Corti F. Editorial: Proteoglycans in the Tumor Microenvironment. Frontiers In Oncology 2022, 12: 872417. PMID: 35463330, PMCID: PMC9021835, DOI: 10.3389/fonc.2022.872417.Peer-Reviewed Original Research
2020
Amyloid-β Precursor Protein APP Down-Regulation Alters Actin Cytoskeleton-Interacting Proteins in Endothelial Cells
Ristori E, Cicaloni V, Salvini L, Tinti L, Tinti C, Simons M, Corti F, Donnini S, Ziche M. Amyloid-β Precursor Protein APP Down-Regulation Alters Actin Cytoskeleton-Interacting Proteins in Endothelial Cells. Cells 2020, 9: 2506. PMID: 33228083, PMCID: PMC7699411, DOI: 10.3390/cells9112506.Peer-Reviewed Original ResearchConceptsAmyloid-β precursor proteinCerebral amyloid angiopathyUbiquitous membrane proteinsFocal adhesion stabilityEndothelial cellsMajor cellular targetInteracting proteinActin cytoskeletonProteomic approachMembrane proteinsAlzheimer's diseaseMolecular mechanismsCellular responsesCellular targetsPhysiological roleRole of APPEndothelial cell proliferationPrecursor proteinCell proliferationNormal endothelial functionProteinNeuronal tissueGrowth factorExogenous stimuliExpression
2019
Publisher Correction: N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization
Corti F, Wang Y, Rhodes JM, Atri D, Archer-Hartmann S, Zhang J, Zhuang ZW, Chen D, Wang T, Wang Z, Azadi P, Simons M. Publisher Correction: N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization. Nature Communications 2019, 10: 2124. PMID: 31064993, PMCID: PMC6504881, DOI: 10.1038/s41467-019-10205-0.Peer-Reviewed Original Research
2018
Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1
Terzuoli E, Corti F, Nannelli G, Giachetti A, Donnini S, Ziche M. Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1. International Journal Of Molecular Sciences 2018, 19: 2638. PMID: 30200598, PMCID: PMC6163484, DOI: 10.3390/ijms19092638.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptor 1Human umbilical vein endothelial cellsCell permeabilityEndothelial cellsFGFR-1 phosphorylationEndothelial cell permeabilityFGF-2 signalingFGF-2 pathwaysFGF-2/FGFRFGFR-1 inhibitorsC-SrcGrowth factor receptor 1Umbilical vein endothelial cellsDownstream signalingHuman endothelial cellsGrowth factor 2Vein endothelial cellsFactor receptor 1Cell migrationFGF-2 upregulationAmplification loopSignalingFactor 2Angiogenic disordersBradykinin B2 receptorPeptides derived from the histidine–proline rich glycoprotein bind copper ions and exhibit anti-angiogenic properties
Magrì A, Grasso G, Corti F, Finetti F, Greco V, Santoro AM, Sciuto S, La Mendola D, Morbidelli L, Rizzarelli E. Peptides derived from the histidine–proline rich glycoprotein bind copper ions and exhibit anti-angiogenic properties. Dalton Transactions 2018, 47: 9492-9503. PMID: 29963662, DOI: 10.1039/c8dt01560k.Peer-Reviewed Original ResearchConceptsElectron paramagnetic resonanceCircular dichroismSpray ionization mass spectrometryPotential drug delivery systemElectron spray ionization mass spectrometryMeans of potentiometryIonization mass spectrometryDrug delivery systemsAmidic bondCopper ionsRole of copperParamagnetic resonanceMass spectrometryComplex speciesTrehalose derivativesProdrug systemEnzymatic degradationDelivery systemCopperPeptidesPotentiometryBondsUVSpectrometryDichroismThe Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling
Kofler N, Corti F, Rivera-Molina F, Deng Y, Toomre D, Simons M. The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. Journal Of Biological Chemistry 2018, 293: 4805-4817. PMID: 29425100, PMCID: PMC5880142, DOI: 10.1074/jbc.m117.812172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndosomesEndothelial CellsMiceMice, Inbred BALB CProtein TransportProtein Tyrosine Phosphatase, Non-Receptor Type 1Rab GTP-Binding ProteinsRab4 GTP-Binding ProteinsRab7 GTP-Binding ProteinsSignal TransductionVascular Endothelial Growth Factor Receptor-2Vesicular Transport ProteinsConceptsEndosomal traffickingVascular endothelial growth factor receptor 2Phosphotyrosine phosphatase 1BVEGFR2 traffickingEndothelial growth factor receptor 2Small GTPase Rab4Rab effector proteinsEndothelial cell functionRab7-positive endosomesCell functionRab GTPaseSorting endosomesCell surface expressionMaster regulatorEndosomal compartmentsVEGFR2 degradationPhosphatase 1BRABEP2Dependent signalingVascular developmentVEGFR2 signalingHigh-resolution microscopyTraffickingEndosomesBiochemical assays
2016
Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development
Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development 2016, 143: 4441-4451. PMID: 27789626, PMCID: PMC5201046, DOI: 10.1242/dev.140129.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsPlanar cell polarity protein Vangl2Lymphatic vessel remodelingMouse embryonic developmentHuman lymphatic endothelial cellsVangl2 overexpressionVangl2 expressionEmbryonic developmentValve morphogenesisEndothelial cellsVasculature developmentSyndecan-4Lymphatic vasculatureFluid shear stressSDC4Double knockout miceMice resultsHigh expressionVessel remodelingLymphatic vesselsExpressionVangl2RemodelingCellsMorphogenesis
2015
Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling
Landskroner-Eiger S, Qiu C, Perrotta P, Siragusa M, Lee MY, Ulrich V, Luciano AK, Zhuang ZW, Corti F, Simons M, Montgomery RL, Wu D, Yu J, Sessa WC. Endothelial miR-17∼92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 12812-12817. PMID: 26417068, PMCID: PMC4611600, DOI: 10.1073/pnas.1507094112.Peer-Reviewed Original Research
2014
E‐NTPDase1/CD39 modulates renin release from heart mast cells during ischemia/reperfusion: a novel cardioprotective role
Aldi S, Marino A, Tomita K, Corti F, Anand R, Olson KE, Marcus AJ, Levi R. E‐NTPDase1/CD39 modulates renin release from heart mast cells during ischemia/reperfusion: a novel cardioprotective role. The FASEB Journal 2014, 29: 61-69. PMID: 25318477, PMCID: PMC4285537, DOI: 10.1096/fj.14-261867.Peer-Reviewed Original ResearchConceptsRenin releaseRenin-angiotensin systemMast cellsVentricular fibrillationRAS activationHMC-1Murine bone marrow-derived mast cellsLocal renin-angiotensin systemBone marrow-derived mast cellsCardiac mast cellsNovel cardioprotective roleMarrow-derived mast cellsPurinergic P2X7 receptorIschemia/reperfusionHeart mast cellsCD39 inhibitionCD39 overexpressionP2X7R blockadeNorepinephrine overflowCardioprotective effectsCardioprotective roleP2X7 receptorCD39Pharmacological inhibitionATP release
2013
Mitochondrial aldehyde dehydrogenase-2 activation prevents β-amyloid-induced endothelial cell dysfunction and restores angiogenesis
Solito R, Corti F, Chen C, Mochly-Rosen D, Giachetti A, Ziche M, Donnini S. Mitochondrial aldehyde dehydrogenase-2 activation prevents β-amyloid-induced endothelial cell dysfunction and restores angiogenesis. Journal Of Cell Science 2013, 126: 1952-1961. PMID: 23447675, PMCID: PMC3666252, DOI: 10.1242/jcs.117184.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase, MitochondrialAmyloid beta-PeptidesBenzamidesBenzodioxolesBeta CateninEnzyme ActivationEnzyme ActivatorsHuman Umbilical Vein Endothelial CellsHumansMembrane PotentialsMitochondrial ProteinsNeovascularization, PhysiologicOxidative StressPeptide FragmentsPhosphorylationReactive Oxygen Species
2011
The Expression Level of Ecto-NTP Diphosphohydrolase1/CD39 Modulates Exocytotic and Ischemic Release of Neurotransmitters in a Cellular Model of Sympathetic Neurons
Corti F, Olson K, Marcus A, Levi R. The Expression Level of Ecto-NTP Diphosphohydrolase1/CD39 Modulates Exocytotic and Ischemic Release of Neurotransmitters in a Cellular Model of Sympathetic Neurons. Journal Of Pharmacology And Experimental Therapeutics 2011, 337: 524-532. PMID: 21325440, PMCID: PMC3083107, DOI: 10.1124/jpet.111.179994.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAntigens, CDApyraseBlotting, WesternDNA PrimersDopamineExocytosisGene Expression Regulation, EnzymologicGene SilencingIschemiaNerve Growth FactorsNeuronsNeurotransmitter AgentsNorepinephrinePC12 CellsPotassiumRatsReceptors, Purinergic P2XReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSympathetic Nervous SystemConceptsE-NTPDase1/CD39CD39 expressionTransmitter ATPSympathetic neuronsDopamine releaseExcessive catecholamine releaseNerve growth factor-differentiated PC12 cellsSympathetic nerve terminalsPC12 cellsExocytosis of ATPCellular modelRelease of ATPCD39 overexpressionIschemic releasePrejunctional siteSympathetic nervesCardiac dysfunctionMyocardial ischemiaCatecholamine releaseCD39 deletionNerve terminalsDepolarization-induced exocytosisAutocrine mannerDiphosphohydrolase-1Predominant catecholamine
2010
Aldehyde Dehydrogenase Activation Prevents Reperfusion Arrhythmias by Inhibiting Local Renin Release From Cardiac Mast Cells
Koda K, Salazar-Rodriguez M, Corti F, Chan NY, Estephan R, Silver RB, Mochly-Rosen D, Levi R. Aldehyde Dehydrogenase Activation Prevents Reperfusion Arrhythmias by Inhibiting Local Renin Release From Cardiac Mast Cells. Circulation 2010, 122: 771-781. PMID: 20697027, PMCID: PMC2927811, DOI: 10.1161/circulationaha.110.952481.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAnimalsArrhythmias, CardiacCell DegranulationCell Line, TumorEnzyme ActivationGuinea PigsHumansIschemic Preconditioning, MyocardialMaleMast CellsMyocardial Reperfusion InjuryMyocytes, CardiacProtein Kinase C-epsilonReceptor, Adenosine A2BReceptor, Adenosine A3ReninRenin-Angiotensin SystemConceptsCardiac mast cellsAnti-RA effectRenin-angiotensin systemAldehyde dehydrogenase type 2Ischemic preconditioningIschemia/reperfusionMast cellsRenin releaseALDH2 activationReperfusion arrhythmiasNorepinephrine releaseRAS activationHMC-1Local renin-angiotensin systemBlockade of adenosineLocal RAS activationClassic ischemic preconditioningDehydrogenase type 2New therapeutic targetsCultured mast cellsPKCepsilon inhibitionFibrillation durationMyocardial ischemiaVentricular tachycardiaHearts ex vivoInteraction between Sensory C-fibers and Cardiac Mast Cells in Ischemia/Reperfusion: Activation of a Local Renin-Angiotensin System Culminating in Severe Arrhythmic Dysfunction
Morrey C, Brazin J, Seyedi N, Corti F, Silver RB, Levi R. Interaction between Sensory C-fibers and Cardiac Mast Cells in Ischemia/Reperfusion: Activation of a Local Renin-Angiotensin System Culminating in Severe Arrhythmic Dysfunction. Journal Of Pharmacology And Experimental Therapeutics 2010, 335: 76-84. PMID: 20668055, PMCID: PMC2957783, DOI: 10.1124/jpet.110.172262.Peer-Reviewed Original ResearchMeSH KeywordsAldehydesAnimalsArrhythmias, CardiacBeta-N-AcetylhexosaminidasesCalcitonin Gene-Related PeptideCell DegranulationCells, CulturedFluorescent Antibody TechniqueGuinea PigsIn Vitro TechniquesMaleMast CellsMyocardial Reperfusion InjuryMyocardiumNerve EndingsNerve Fibers, UnmyelinatedNorepinephrineReninRenin-Angiotensin SystemSensory Receptor CellsSubstance PSynaptosomesConceptsRenin-angiotensin systemIschemia/reperfusionCardiac mast cellsSubstance P receptor blockadeLocal renin-angiotensin systemSubstance PMast cellsSensory nervesCultured mast cellsRenin releaseReceptor blockadeCardiac dysfunctionLocal cardiac renin-angiotensin systemCardiac renin-angiotensin systemCardiac nerve terminalsCardiac sensory nervesMast cell reninSubstance P releaseSensory C-fibersMast cell stabilizationSubstance P receptorCardiac synaptosomesReperfusion arrhythmiasNorepinephrine overflowAngiotensin production