2024
Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells
Geraldo L, Xu Y, Mouthon G, Furtado J, Leser F, Blazer L, Adams J, Zhang S, Zheng L, Song E, Robinson M, Thomas J, Sidhu S, Eichmann A. Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells. Science Translational Medicine 2024, 16: eadn8388. PMID: 39565875, DOI: 10.1126/scitranslmed.adn8388.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCorneal NeovascularizationDisease Models, AnimalHumansIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMyeloid CellsNeovascularization, PathologicNerve Tissue ProteinsReceptors, ImmunologicRetinaRetinal NeovascularizationSignal TransductionConceptsOxygen-induced retinopathyPathological ocular neovascularizationCorneal neovascularizationMyeloid cellsOcular neovascularizationHeterogeneous population of myeloid cellsBlood-retina barrier integrityPopulation of myeloid cellsActivation of myeloid cellsMonoclonal antibodiesOcular neovascular diseasesBlinding eye diseaseHuman monoclonal antibodyExtracellular domainMouse model in vivoModel in vivoMAb treatmentMyeloid populationsOIR retinasNeovascular diseasesVision lossEye diseaseSlit-RoboSlit-Robo signalingBlocking antibodiesZonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature
Del Gaudio I, Nitzsche A, Boyé K, Bonnin P, Poulet M, Nguyen T, Couty L, Ha H, Nguyen D, Cazenave-Gassiot A, Alaya K, Thérond P, Chun J, Wenk M, Proia R, Henrion D, Nguyen L, Eichmann A, Camerer E. Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature. Cardiovascular Research 2024, 120: 1794-1810. PMID: 39086170, PMCID: PMC11587562, DOI: 10.1093/cvr/cvae168.Peer-Reviewed Original ResearchHigh endothelial venulesS1PR1 signalingEndothelial functionS1P productionDisease states associated with endothelial dysfunctionPlasma S1PDose-dependentlyLymphatic vasculatureEndothelial cellsResistance-sized arteriesLevels of sphingosine 1-phosphateLung capillariesS1P receptor 1Sphingosine 1-phosphateImmunosuppressive therapyLigand-independent mechanismResistance arteriesLymph nodesDeficient miceAlbumin extravasationHematopoietic cellsCirculating levelsEndothelial dysfunctionS1P releaseCirculating biomarkersThe interactions between energy homeostasis and neurovascular plasticity
Chen B, de Launoit E, Meseguer D, Garcia Caceres C, Eichmann A, Renier N, Schneeberger M. The interactions between energy homeostasis and neurovascular plasticity. Nature Reviews Endocrinology 2024, 20: 749-759. PMID: 39054359, DOI: 10.1038/s41574-024-01021-8.Peer-Reviewed Original ResearchWestern dietLifestyle interventionNeurovascular systemCurrent obesity epidemicEnergy homeostasisStable body weightLocal neuronal networksRegulate energy balanceNeuronal networksFood intakeObesity epidemicSedentary lifestylePharmacological interventionsNeurovascular plasticityOverall healthNutritional milieuWeight lossLong-term needsCardiovascular systemBody weightEnergy expenditureAdverse effectsBrain centresLifestyleBrain vasculatureACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature
Pak B, Kim M, Han O, Lee H, Dubrac A, Choi W, Yang J, Boyé K, Cho H, Citrin K, Kim I, Eichmann A, Bautch V, Jin S. ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature. Angiogenesis 2024, 27: 765-777. PMID: 38955953, DOI: 10.1007/s10456-024-09936-6.Peer-Reviewed Original ResearchBone morphogenetic proteinVenous endotheliumProliferation of endotheliumBone morphogenetic protein signalingRetinal vesselsActivin A type I receptorExpression of CDKN1A/p21Bone morphogenetic protein receptorProliferation of endothelial cellsCell cycle progressionRetinal vasculatureEndothelial proliferationACVR1/ALK2I receptorEndotheliumEndothelial cellsCycle progressionModulate angiogenesisActive proliferationMorphogenetic proteinsProliferationContext of angiogenesisAngiogenesisVasculatureCDKN1A/p21Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching
Raza Q, Nadeem T, Youn S, Swaminathan B, Gupta A, Sargis T, Du J, Cuervo H, Eichmann A, Ackerman S, Naiche L, Kitajewski J. Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching. Scientific Reports 2024, 14: 13603. PMID: 38866944, PMCID: PMC11169293, DOI: 10.1038/s41598-024-64375-z.Peer-Reviewed Original ResearchConceptsNotch signalingEndothelial cell behaviorEndothelial junctionsCell behaviorMultiple endothelial cell typesStabilization of endothelial junctionsNotch activationEndothelial Notch signalingTarget of Notch signalingTranscriptional activation complexEndothelial cell typesPlexus branchesVascular densityEndothelial proliferationBrain endotheliumMouse retinaIn vivo targetingEffector proteinsVascular outgrowthJunction activityNotch proteinsEndothelial cellsExcessive vascularizationDownstream effectorsEndothelial gene expressionVEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Boisserand L, Geraldo L, Bouchart J, Kamouh M, Lee S, Sanganahalli B, Spajer M, Zhang S, Lee S, Parent M, Xue Y, Skarica M, Yin X, Guegan J, Boyé K, Leser F, Jacob L, Poulet M, Li M, Liu X, Velazquez S, Singhabahu R, Robinson M, Askenase M, Osherov A, Sestan N, Zhou J, Alitalo K, Song E, Eichmann A, Sansing L, Benveniste H, Hyder F, Thomas J. VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. Journal Of Experimental Medicine 2024, 221: e20221983. PMID: 38442272, PMCID: PMC10913814, DOI: 10.1084/jem.20221983.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor-CDeep cervical lymph nodesCentral nervous systemEffect of vascular endothelial growth factor-CMeningeal lymphatic vesselsAmeliorated motor performanceCervical lymph nodesIschemic strokeVEGF-C overexpressionIncreased BDNF signalingAcute ischemic strokeBrain cellsIncreased CSF drainageIschemic stroke outcomesModel of ischemic strokeMouse model of ischemic strokeImmune surveillanceCSF drainageLymph nodesFluid drainageNucleus RNA sequencingLymphatic growthLymphatic drainageMouse modelBDNF signalingComplementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow
Poulos M, Ramalingam P, Winiarski A, Gutkin M, Katsnelson L, Carter C, Pibouin-Fragner L, Eichmann A, Thomas J, Miquerol L, Butler J. Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow. Stem Cell Reviews And Reports 2024, 20: 1135-1149. PMID: 38438768, PMCID: PMC11087254, DOI: 10.1007/s12015-024-10703-9.Peer-Reviewed Original ResearchBone marrowEndothelial cellsMouse modelAdult bone marrowArteriole endothelial cellsAdult BMOff-target activityHematopoietic dysfunctionAdult marrowHematopoietic homeostasisEndothelial cell subtypesVascular subtypeCre-expressing lineEndothelial subtypesEndothelial-specificMouse linesHSC activationCell subtypesEC subtypesParacrine signalingPerivascular cellsModulate HSC activationMarrowSubtypesAdult endotheliumVascular development, remodeling and maturation
Furtado J, Eichmann A. Vascular development, remodeling and maturation. Current Topics In Developmental Biology 2024, 159: 344-370. PMID: 38729681, DOI: 10.1016/bs.ctdb.2024.02.001.Peer-Reviewed Original ResearchGene expression patternsKnowledge of vascular biologyControlling nutrient uptakeEarly embryonic developmentDysfunctional vasculatureVascular systemVascular system developmentSystem dysfunctionExpression patternsOrgan physiologyFunctional circulatory systemEndothelial cellsTherapeutic potentialEmbryonic developmentVascular system dysfunctionNutrient uptakeBlood vesselsSemi-permeable barrierVascular biologyHuman morbidityCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signalStromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy
Liu X, Li B, Wang S, Zhang E, Schultz M, Touma M, Da Rocha A, Evans S, Eichmann A, Herron T, Chen R, Xiong D, Jaworski A, Weiss S, Si M. Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. Circulation Research 2024, 134: 913-930. PMID: 38414132, PMCID: PMC10977056, DOI: 10.1161/circresaha.122.321292.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionAortic constrictionPressure overloadCardiomyocyte hypertrophyVascular mural cellsCardiomyocyte hypertrophy in vitroDecreased left ventricular hypertrophyStimulate cardiomyocyte hypertrophyCongenital heart defectsCell-specific knockoutLeft ventricular functionAdverse cardiac remodelingVentricular pressure overloadCardiomyocyte-specific deletionMural cellsHypertrophy in vitroPressure overload stressCardiac stromal cellsMyocardial tissue samplesEffects in vitroIn vitro studiesHypertrophy-related genesHeart defectsRegulate cardiac developmentVentricular function
2023
Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu X, le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas J, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2023, 625: e12-e12. PMID: 38110575, DOI: 10.1038/s41586-023-06944-2.Peer-Reviewed Original ResearchThe Lefoulon Delalande Foundation honors the lymphatic vascular system
Eichmann A. The Lefoulon Delalande Foundation honors the lymphatic vascular system. Bleeding Thrombosis And Vascular Biology 2023, 2 DOI: 10.4081/btvb.2023.99.Peer-Reviewed Original ResearchChylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption
Zarkada G, Chen X, Zhou X, Lange M, Zeng L, Lv W, Zhang X, Li Y, Zhou W, Liu K, Chen D, Ricard N, Liao J, Kim Y, Benedito R, Claesson-Welsh L, Alitalo K, Simons M, Ju R, Li X, Eichmann A, Zhang F. Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption. Circulation Research 2023, 133: 333-349. PMID: 37462027, PMCID: PMC10530007, DOI: 10.1161/circresaha.123.322607.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsCell-cell junctionsCytoskeleton contractionMolecular biology approachesSmall GTPase Rac1Cytoskeletal contractilityBiology approachGTPase Rac1Stress fibersA SignalingPI3KLipid uptakePermeability regulationLymphatic permeabilityIntestinal lipid absorptionLEC junctionJunction openingEndothelial cellsLymphatic capillariesVEGFR-2Fundamental mechanismsLymphatic barrierLymphatic vesselsVascular endothelial growthLymphatic junctionsCCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma
Geraldo L, Garcia C, Xu Y, Leser F, Grimaldi I, de Camargo Magalhães E, Dejaegher J, Solie L, Pereira C, Correia A, De Vleeschouwer S, Tavitian B, Canedo N, Mathivet T, Thomas J, Eichmann A, Lima F. CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma. Cellular And Molecular Life Sciences 2023, 80: 179. PMID: 37314567, PMCID: PMC10267017, DOI: 10.1007/s00018-023-04788-7.Peer-Reviewed Original ResearchConceptsMicroglia/macrophage recruitmentC chemokine receptor type 7CCL21-CCR7Central nervous systemMacrophage recruitmentTumor microenvironmentChemokine receptor type 7Fatal primary tumorMouse GBM modelsChemokine ligand 21Potential therapeutic targetVEGF-A productionTumor cell deathCCR7 expressionTherapeutic optionsPrimary tumorPoor survivalCurrent treatmentGBM patientsTumor cell migrationTherapeutic targetBrain cancerNervous systemChemotherapy resistanceLigand 21Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Lee S, Schleer H, Park H, Jang E, Boyer M, Tao B, Gamez-Mendez A, Singh A, Folta-Stogniew E, Zhang X, Qin L, Xiao X, Xu L, Zhang J, Hu X, Pashos E, Tellides G, Shaul P, Lee W, Fernandez-Hernando C, Eichmann A, Sessa W. Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2023, 2: 438-448. PMID: 39196046, PMCID: PMC11358031, DOI: 10.1038/s44161-023-00266-2.Peer-Reviewed Original ResearchLDL transcytosisLDL receptor knockout miceReceptor knockout miceAtherosclerotic cardiovascular diseaseLow-density lipoprotein accumulationHigh-fat dietPromising therapeutic strategyTherapeutic neutralizationMacrophage infiltrationTriglyceride levelsLDL entryCardiovascular diseaseSelective monoclonal antibodiesLipoprotein accumulationTherapeutic strategiesKnockout micePlaque formationAtherosclerosis initiationType 1Genetic deletionArterial wallMonoclonal antibodiesEndothelial cellsLDL accumulationMiceConnexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone
Genet N, Genet G, Chavkin N, Paila U, Fang J, Vasavada H, Goldberg J, Acharya B, Bhatt N, Baker K, McDonnell S, Huba M, Sankaranarayanan D, Ma G, Eichmann A, Thomas J, Ffrench-Constant C, Hirschi K. Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone. Cell Reports 2023, 42: 112371. PMID: 37043357, PMCID: PMC10564973, DOI: 10.1016/j.celrep.2023.112371.Peer-Reviewed Original ResearchConceptsSubventricular zoneEndothelial cellsNSC proliferationNSC quiescenceAdult brain subventricular zoneBlood-brain barrierBrain subventricular zoneStem cell therapyNeural stem cell nicheNeurovascular interactionsNeuroblast generationAdult brainSingle-cell RNA sequencingNeurodegenerative disordersChannel-independent mannerCell therapySVZ-NSCsConnexin 43Expression of genesERK activationNSC regulationNSC behaviorRNA sequencingCx43Proliferation
2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformationsChapter 22 Sprouting angiogenesis in vascular and lymphatic development
Eichmann A, Li J. Chapter 22 Sprouting angiogenesis in vascular and lymphatic development. 2022, 265-273. DOI: 10.1016/b978-0-12-822546-2.00006-x.Chapters
2021
Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development
Li J, Geraldo LH, Dubrac A, Zarkada G, Eichmann A. Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development. Journal Of The American Society Of Nephrology 2021, 32: 2255-2272. PMID: 34341180, PMCID: PMC8729857, DOI: 10.1681/asn.2020111640.Peer-Reviewed Original ResearchConceptsGlomerular vascularizationRobo receptorsKidney functionVascular developmentGlomerular perfusionKidney diseaseGlomerular endotheliumLigand trapInhibited vascularizationSlit2-RoboEndothelial proliferationGlomerular capillariesEndothelial compartmentGlomerular angiogenesisPerfusion analysisKidney vasculatureVascularizationUreteric bud branchingNovel roleAxon guidanceNephron developmentBlood filtrationReceptorsAngiogenesisGene deletionStop the Divide and Build Coronary Arteries
Zarkada G, Eichmann A. Stop the Divide and Build Coronary Arteries. Developmental Cell 2021, 56: 255-256. PMID: 33561420, DOI: 10.1016/j.devcel.2021.01.008.Commentaries, Editorials and Letters