2025
Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis
Zhang T, Huang X, Goodwin J, Wen R, Liu Y, Yang Y, Zhang T, Zheng Y, Chen A, Hao P, Tong X, Yang N, Liu C. Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science Advances 2025, 11: eadt7589. PMID: 40498836, PMCID: PMC12154197, DOI: 10.1126/sciadv.adt7589.Peer-Reviewed Original ResearchConceptsVascular leakagePuncture (CLP)-induced polymicrobial sepsisRegulating endothelial barrier functionCLP-challenged miceEndothelial barrier dysfunctionTrans-endothelial electrical resistanceEndothelial barrier functionLipopolysaccharide (LPS)-induced endotoxemiaVascular endothelial cellsPattern recognition receptorsSurvival benefitMultiorgan failurePolymicrobial sepsisTrans-endothelial migrationCecal ligationBacterial pneumoniaLung injuryBarrier dysfunctionVascular injurySingle-cell RNA sequencingDecreased mortalityInflammatory stormBacterial infectionsHeterogeneity of vascular endothelial cellsSepsisTranscriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease
Fließer E, Jandl K, Chen S, Wang M, Schupp J, Kuebler W, Baker A, Kwapiszewska G. Transcriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease. JCI Insight 2025, 10: e191059. PMID: 40401523, PMCID: PMC12128986, DOI: 10.1172/jci.insight.191059.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndothelial CellsHumansImmunomodulationLungLung DiseasesSingle-Cell AnalysisTranscriptomeConceptsEndothelial cellsCardiopulmonary vasculatureImmune responseImmune cell recruitmentRegulation of immune responsesFunction of endothelial cellsImmunoregulatory roleAntigen presentationCytokine secretionCell recruitmentCardiopulmonary healthDelivery of oxygenSingle-cell RNA sequencingImmunomodulatory propertiesCardiopulmonary diseaseClearance functionDisease pathogenesisTherapy targetTranscriptional signatureEC subpopulationsImmunomodulatory activityDiseaseLungVasculatureHeartHypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression
Harada A, Yasumizu Y, Harada T, Fumoto K, Sato A, Maehara N, Sada R, Matsumoto S, Nishina T, Takeda K, Morii E, Kayama H, Kikuchi A. Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression. Nature Communications 2025, 16: 3653. PMID: 40246836, PMCID: PMC12006413, DOI: 10.1038/s41467-025-58748-9.Peer-Reviewed Original ResearchConceptsColon cancer progressionSingle-cell RNA-seq dataCancer progressionEndothelial cellsRNA-seq dataColon cancer aggressivenessSuppression of angiogenesisColon cancer growthColon cancer formationCancer aggressivenessInflammatory fibroblastsVEGF receptor1Cancer growthPromote tumorigenesisCancer formationWnt5aMeta-analysisWnt ligandsLuminal sideFibroblast subtypesColonHypoxic environmentFibroblastsCellsFluid Shear Stress–Regulated Vascular Remodeling: Past, Present, and Future
Deng H, Eichmann A, Schwartz M. Fluid Shear Stress–Regulated Vascular Remodeling: Past, Present, and Future. Arteriosclerosis Thrombosis And Vascular Biology 2025, 45: 882-900. PMID: 40207366, PMCID: PMC12094896, DOI: 10.1161/atvbaha.125.322557.Peer-Reviewed Original ResearchConceptsFluid shear stressShear stressVascular remodelingVascular bedCapillary densityOutward remodelingIn vivo animal modelsPotential therapeutic interventionsDownstream vascular bedArterial toneTherapeutic strategiesAnimal modelsPerfusion of tissuesAdequate perfusionUpstream arteriesEndothelial cellsVascular diseaseBlood flowTherapeutic interventionsClinical implicationsBlood vesselsTreat vascular diseasesFlowMetabolic stressBloodReduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cellsMigration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines
Parween F, Singh S, Kathuria N, Zhang H, Ashida S, Otaizo-Carrasquero F, Shamsaddini A, Gardina P, Ganesan S, Kabat J, Lorenzi H, Riley D, Myers T, Pittaluga S, Bielekova B, Farber J. Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines. Nature Communications 2025, 16: 1978. PMID: 40000641, PMCID: PMC11861662, DOI: 10.1038/s41467-025-57002-6.Peer-Reviewed Original ResearchConceptsEndothelial cellsTransendothelial migrationCCR2 ligandsFunction of CCR6Migration arrestChemokine receptor CCR6T cell receptor activationCerebrospinal fluid of patientsActivation-associated genesFluid of patientsActivated endothelial cellsEC surfaceTh17 signatureReceptor CCR6Th17 cellsT cellsChemokine receptorsCell extravasationInflammatory cytokinesReceptor activationCerebrospinal fluidCCR6ChemokinesMultiple sclerosisEnhanced expressionSuppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disordersEndothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling
Kim Y, Kim M, Kim S, Lee R, Ujihara Y, Marquez-Wilkins E, Jiang Y, Yang E, Kim H, Lee C, Park C, Kim I. Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling. Nature Communications 2025, 16: 1407. PMID: 39915488, PMCID: PMC11802743, DOI: 10.1038/s41467-025-56720-1.Peer-Reviewed Original ResearchConceptsBlood-brain barrierNeuronal excitabilityB-cateninBarrier functionMouse blood-brain barrierReduced neuronal excitabilityMale mutant miceBlood-brain barrier permeabilityBrain endothelial cellsAutism spectrum disorderNeonatal micePotential therapeutic targetASD risk genesMutant miceTight junctionsImpaired sociabilityPathogenic mechanismsBrain parenchymaEndothelial cellsTherapeutic targetASD pathogenesisSHANK3Adult ageDisabling conditionMicePharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage
Schlosser A, Pilecki B, Allen C, Benest A, Lynch A, Hua J, Ved N, Blackley Z, Andersen T, Hennig D, Graversen J, Möller S, Skallerup S, Ormhøj M, Lange C, Agostini H, Grauslund J, Heegaard S, Dacheva I, Koss M, Hu W, Iglesias B, Lawrence M, Beck H, Steffensen L, Laursen N, Andersen G, Holmskov U, Bates D, Sorensen G. Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage. Molecular Therapy 2025, 33: 1048-1072. PMID: 39863929, PMCID: PMC11897753, DOI: 10.1016/j.ymthe.2025.01.038.Peer-Reviewed Original ResearchConceptsMicrofibrillar-associated protein 4Vascular leakageNeovascular age-related macular degenerationAge-related macular degenerationChoroidal neovascularization mouse modelDiabetic macular edemaProtein 4Treatment of neovascularizationLaser-induced choroidal neovascularization mouse modelVascular leakage areaDuration of efficacyVascular endothelial cellsRetinal neoangiogenesisMacular edemaRetinal neovascularizationMacular degenerationVision lossRetinal diseasesPharmacological blockMuller cellsRetinal astrocytesVascular permeabilityVascular mural cellsEndothelial cell motilityMouse modelcSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling
Deng H, Rukhlenko O, Joshi D, Hu X, Junk P, Tuliakova A, Kholodenko B, Schwartz M. cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling. Science Advances 2025, 11: eado9970. PMID: 39752487, PMCID: PMC11698091, DOI: 10.1126/sciadv.ado9970.Peer-Reviewed Original ResearchConceptsShear stressCell cycle-dependent kinasesHigh shear stressLow shear stressOscillatory shear stressPhysiological shear stressFluid shear stressCell cycle arrestRegulatory networksTranscriptomic statesResponse to drug treatmentCycle arrestCell cycleEndothelial cell cycleDisease susceptibilityRegulatory mechanismsVessel behaviorCDK2Endothelial cellsIn vitroStressRegulationVascular endothelial cellsRemodelingCells
2024
Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity
Furtado J, Geraldo L, Leser F, Bartkowiak B, Poulet M, Park H, Robinson M, Pibouin-Fragner L, Eichmann A, Boyé K. Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408674121. PMID: 39693351, PMCID: PMC11670198, DOI: 10.1073/pnas.2408674121.Peer-Reviewed Original ResearchConceptsBlood-retina barrierBlood-retina barrier integrityGene expressionScRNA-seqEndothelial cellsNetrin-1 receptor UNC5BNetrin-1Cell gene expression programsSingle-cell RNA sequencingDevelopment of retinal diseasesWnt signaling componentsGene expression programsTight junction proteinsMutant endothelial cellsScaffold proteinTranscriptional activityLoss of functionRNA sequencingRetinal arteriolesRetina endothelial cellsRetinal diseasesHomologue 1Expression programsReceptor UNC5BEndothelial subtypesShear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques
Zhou Z, Korteland S, Tardajos-Ayllon B, Wu J, Chambers E, Weninck J, Simons M, Dunning M, Schenkel T, Diagbouga M, Wentzel J, Fragiadaki M, Evans P. Shear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques. Atherosclerosis 2024, 398: 118622. PMID: 39413592, DOI: 10.1016/j.atherosclerosis.2024.118622.Peer-Reviewed Original ResearchConceptsShear stressPhysiological shear stressComputational fluid dynamicsDiseased arteriesHealthy arteriesGene Ontology termsFluid dynamicsSingle-cell RNA sequencingApoptotic gene expressionEffect of physiological shear stressPromote vascular homeostasisOntology termsRNA sequencingFunctional enrichmentEndothelial cellsGene expressionRisk of cardiovascular complicationsEndothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studiesHemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis
Cheng S, Xia I, Wanner R, Abello J, Stratman A, Nicoli S. Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis. ELife 2024, 13: rp94094. PMID: 38985140, PMCID: PMC11236418, DOI: 10.7554/elife.94094.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCircle of WillisEndothelial CellsHemodynamicsHumansMuscle, Smooth, VascularMyocytes, Smooth MuscleZebrafishConceptsVascular smooth muscle cellsWall shear stressVascular smooth muscle cell differentiationVSMC differentiationEndothelial cellsAnalysis of blood flowBlood flowShear stressBrain arteriesPulsatile flowCerebrovascular diseaseDedifferentiated vascular smooth muscle cellsRegulate cerebral blood flowSmooth muscle cellsRed blood cell velocityDedifferentiation of vascular smooth muscle cellsCerebral blood flowBlood cell velocityArterial muscularizationVenous plexusCell progenitorsMuscle cellsBlood flow activationArteryFlowProcoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19
Cadamuro M, Lasagni A, Radu C, Calistri A, Pilan M, Valle C, Bonaffini P, Vitiello A, Toffanin S, Venturin C, Friòn-Herrera Y, Sironi S, Alessio M, Previtali G, Seghezzi M, Gianatti A, Strazzabosco M, Strain A, Campello E, Spiezia L, Palù G, Frigo A, Tosoni A, Nebuloni M, Parolin C, Sonzogni A, Simioni P, Fabris L. Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19. Journal Of Hepatology 2024, 81: 872-885. PMID: 38908437, DOI: 10.1016/j.jhep.2024.06.014.Peer-Reviewed Original ResearchConceptsIntrapulmonary vascular dilatationWorsening respiratory failureSARS-CoV-2 infectionRespiratory failureFatal COVID-19Procoagulant phenotypeSARS-CoV-2Development of intrapulmonary vascular dilatationsVascular dilatationAssociated with portal thrombosisComplication of COVID-19 infectionTissue factorWork-up of patientsHuman pulmonary microvascular endothelial cellsEndothelial cellsObliterative portal venopathyPulmonary microvascular endothelial cellsAbsence of cirrhosisFatal respiratory failureAssociated with younger ageSevere liver diseaseDevelopment of hypoxemiaPathophysiology of thrombosisPortal vein branchesSevere COVID-19Notch 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 expressionDirect conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg
Farber G, Dong Y, Wang Q, Rathod M, Wang H, Dixit M, Keepers B, Xie Y, Butz K, Polacheck W, Liu J, Qian L. Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg. Nature Communications 2024, 15: 4170. PMID: 38755186, PMCID: PMC11098819, DOI: 10.1038/s41467-024-48354-6.Peer-Reviewed Original ResearchConceptsCardiac fibroblastsEndothelial cellsEndothelial-like cellsIn vivoRepair injured tissuesFunction in vitroInduced endothelial cellsConversion of cardiac fibroblastsInfarct siteReprogramming strategiesMyocardial infarction siteReprogramming approachInjured tissueInjury resultsVascular perfusionEndothelial-likeScar regionPhysiological function in vitroIn vitroOrgan-specificFibroblastsHeterogeneous populationCellsReprogrammingTranslational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study
Shimbo D, Cohen M, McGoldrick M, Ensari I, Diaz K, Fu J, Duran A, Zhao S, Suls J, Burg M, Chaplin W. Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study. Journal Of The American Heart Association 2024, 13: e032698. PMID: 38690710, PMCID: PMC11179860, DOI: 10.1161/jaha.123.032698.Peer-Reviewed Original ResearchConceptsEndothelial cell-derived microparticlesEndothelium-dependent vasodilationCell-derived microparticlesEndothelial progenitor cellsGroup x time interactionEndothelial cell healthCirculating bone marrow-derived endothelial progenitor cellsIncreased risk of cardiovascular disease eventsIndex scoreEndothelial healthProgenitor cellsImpaired endothelium-dependent vasodilationRisk of cardiovascular disease eventsAcute effectsTime interactionBone marrow-derived endothelial progenitor cellsMarrow-derived endothelial progenitor cellsRecall taskStatistically significant group x time interactionsSignificant group x time interactionRandomized controlled studyCardiovascular disease eventsVascular endothelial healthRandomized controlled experimental studyNegative emotionsDisturbed flow in the juxta-anastomotic area of an arteriovenous fistula correlates with endothelial loss, acute thrombus formation, and neointimal hyperplasia
Bai H, Varsanik M, Thaxton C, Ohashi Y, Gonzalez L, Zhang W, Aoyagi Y, Kano M, Yatsula B, Li Z, Pocivavsek L, Dardik A. Disturbed flow in the juxta-anastomotic area of an arteriovenous fistula correlates with endothelial loss, acute thrombus formation, and neointimal hyperplasia. AJP Heart And Circulatory Physiology 2024, 326: h1446-h1461. PMID: 38578237, PMCID: PMC11380968, DOI: 10.1152/ajpheart.00054.2024.Peer-Reviewed Original ResearchConceptsEndothelial cell lossOutflow veinChronic kidney diseaseJuxta-anastomotic areaMouse AVF modelNeointimal hyperplasiaThrombus formationAcute thrombus formationCell lossHuman AVF maturationGene OntologyAVF maturationAVF patencyEarly thrombus formationArteriovenous fistulaC57BL/6 miceClinical failureWistar ratsEndothelial lossKidney diseaseImmune responseEndothelial cellsHyperplasiaMiceAVFSpatial–temporal order–disorder transition in angiogenic NOTCH signaling controls cell fate specification
Kang T, Bocci F, Nie Q, Onuchic J, Levchenko A. Spatial–temporal order–disorder transition in angiogenic NOTCH signaling controls cell fate specification. ELife 2024, 12: rp89262. PMID: 38376371, PMCID: PMC10942579, DOI: 10.7554/elife.89262.Peer-Reviewed Original ResearchMeSH KeywordsCell CommunicationCell DifferentiationEndothelial CellsMorphogenesisSignal TransductionConceptsCell fate specificationFate specificationNotch signalingMorphogenic processesCell-cell communicationComplex morphogenic processesCell fateDynamics of spatial patternsDepletion of fibronectinTip cellsSprout extensionAngiogenic morphogenesisHypoxic micro-environmentCell plasticityCellsComputational analysisPre-existing onesCell patternMicro-environmentSpatial patternsLocal enrichmentMorphogenesisEndothelial cellsAngiogenesis modelFibronectin
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