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 cellsSepsisPharmacological 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
Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering
Batty L, Park J, Qin L, Riaz M, Lin Y, Xu Z, Gao X, Li X, Lopez C, Zhang W, Hoareau M, Fallon M, Huang Y, Luo H, Luo J, Ménoret S, Li P, Jiang Z, Smith P, Sachs D, Tellides G, Anegon I, Pober J, Liu P, Qyang Y. Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering. Acta Biomaterialia 2024, 193: 171-184. PMID: 39681154, PMCID: PMC12212065, DOI: 10.1016/j.actbio.2024.12.033.Peer-Reviewed Original ResearchInduced pluripotent stem cellsVascular tissue engineeringPig induced pluripotent stem cellsPluripotent stem cellsEndothelial cellsLarge animal modelStem cellsAnimal modelsTissue engineeringInferior vena cava graftHuman induced pluripotent stem cellsEffective differentiation protocolsPreclinical large animal modelExpression of endothelial markersCell-based therapiesExtensive preclinical testingPig endothelial cellsFunctional endothelial cellsIn vivo functional studiesTreatment of cardiovascular diseasesVascular endothelial cellsTissue engineering therapiesTransplant therapeuticsEfficacy of tissueImmunodeficient ratsGenetic and molecular drivers of scleroderma pathogenesis
Odell I. Genetic and molecular drivers of scleroderma pathogenesis. Clinics In Dermatology 2024, 43: 153-159. PMID: 39675445, PMCID: PMC12009687, DOI: 10.1016/j.clindermatol.2024.12.007.Peer-Reviewed Original ResearchGrowth factor signalingFactor signalingScleroderma pathogenesisActivated growth factor receptorsGenetic association studiesTherapeutic approachesMolecular driversHereditary hemorrhagic telangiectasiaAssociation studiesRegulatory genesGrowth factor receptorImmune regulatory genesGenetic studiesBiological insightsVascular endothelial cellsMolecular mechanismsHemorrhagic telangiectasiaImmune dysregulationClinical findingsVascular abnormalitiesHeterogeneous diseaseClinical phenotypeFactor receptorPatient phenotypesMultiple malignanciesElectron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues
Ladinsky M, Zhu L, Ullah I, Uchil P, Kumar P, Kay M, Bjorkman P. Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. Journal Of Virology 2024, 98: e01432-24. PMID: 39475277, PMCID: PMC11575291, DOI: 10.1128/jvi.01432-24.Peer-Reviewed Original ResearchHIV-1 virionsHIV-1 target cellsHIV-1Fusion inhibitorsTarget cellsBone marrow/liver/thymus miceHIV-1 pseudovirionsCo-receptorHost cell membraneTZM-bl cellsPre-hairpin intermediateVascular endothelial cellsCell surfaceHumanized miceTZM-blCell membraneInfected tissuesEnvEndothelial cellsViral envelopeBind host receptorsHost receptorsInhibitorsCo-receptor proteinsPresence of virionsEndothelial 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 studiesThe COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management
Becker R, Tantry U, Khan M, Gurbel P. The COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management. Journal Of Thrombosis And Thrombolysis 2024, 58: 15-49. PMID: 39179952, PMCID: PMC11762605, DOI: 10.1007/s11239-024-03028-4.Peer-Reviewed Original ResearchNeutrophil extracellular trapsMild to moderate illnessHost immunoinflammatory responseOptimal patient managementSARS-CoV-2SARS-CoV-2 infectionEndothelial cell inflammationVascular endothelial cellsSurveillance modalitiesClinical featuresOrgan injuryImmunoinflammatory responseMicrovascular thrombosisInflammatory signatureAtherothrombotic phenotypeCirculating monocytesChronic phasePatient managementVascular eventsAcute phaseExtracellular trapsCritical illnessThrombosisEndothelial cellsMedical literatureIdentification of abnormal airway niches in the fibrotic lung using spatial transcriptomics
Justet A, Ravaglia C, Zhao A, Adams N, Agshin B, Kaminski N, Tomasseti S, Poletti V. Identification of abnormal airway niches in the fibrotic lung using spatial transcriptomics. Revue Des Maladies Respiratoires 2024, 41: 215. DOI: 10.1016/j.rmr.2024.01.068.Peer-Reviewed Original ResearchVascular endothelial cellsIPF patientsIPF lungsEpithelial cellsLung tissueEndothelial cellsCOVID patientsAirway epithelial cellsAbnormal cell populationsAlveolar epithelial cellsProgression to fibrosisLong COVIDBasaloid cellsControl patientsImmune cellsGene panelFFPE slidesFibrotic lungsProximal airwaysPatientsDistal lungLungBasal cellsCell populationsLong COVID patients
2023
Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma
Li Y, Zhao Q, Zhu X, Zhou L, Song P, Liu B, Tian D, Chen Q, Zhou J, Deng G. Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma. CNS Neuroscience & Therapeutics 2023, 30: e14528. PMID: 38044793, PMCID: PMC11017454, DOI: 10.1111/cns.14528.Peer-Reviewed Original ResearchBlood-brain barrierP-gp inhibitorsCerebral vascular endothelial cellsStrong anti-tumor effectsCommon primary malignant tumorApplication of paclitaxelEfflux transportersPrimary malignant tumorsUse of paclitaxelEfficacy of paclitaxelAnti-tumor effectsPeripheral solid tumorsCentral nervous systemNatural bioactive moleculesEffective anti-cancer drugsP-gp transporterVascular endothelial cellsBlood concentrationsMalignant tumorsGlioma treatmentNervous systemP-gpAnti-cancer drugsSolid tumorsTumor tissueHuman vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease
Du Y, de Jong I, Gupta K, Waisbourd-Zinman O, Har-Zahav A, Soroka C, Boyer J, Llewellyn J, Liu C, Naji A, Polacheck W, Wells R. Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease. Biofabrication 2023, 16: 015004. PMID: 37820623, PMCID: PMC10587873, DOI: 10.1088/1758-5090/ad0261.Peer-Reviewed Original ResearchConceptsCholestatic liver diseasePrimary sclerosing cholangitisLiver diseaseBile ductBile duct tissuesDuct tissuePeripheral blood mononuclear cellsEndothelial cellsBlood mononuclear cellsNormal bile duct tissuesHuman vascular endothelial cellsVascular endothelial cellsPSC patientsSclerosing cholangitisIL-17ATh17 cellsMononuclear cellsVascular channelsBiliary organoidsCholangiocyte organoidsBlood vesselsCholangiocytesDiseaseFlow of bloodTight junctionsEndotheliopathy of liver sinusoidal endothelial cells in liver disease
Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathology International 2023, 73: 381-393. PMID: 37589433, DOI: 10.1111/pin.13361.Peer-Reviewed Original ResearchConceptsLiver diseaseSinusoidal endothelial cellsEndothelial cellsLiver injuryLiver tissueIntercellular adhesion molecule-1Improvement of thrombocytopeniaNeutrophil chemotactic mediatorsChronic hepatitis CLiver sinusoidal endothelial cellsSetting of inflammationSevere hepatic inflammationAdhesion molecule-1Largest solid organPotential therapeutic strategyVascular endothelial cellsVon Willebrand factorHepatitis CNeutrophil accumulationHepatic inflammationChemotactic mediatorsIL-6Antithrombotic factorsChemokine ligandSolid organsAtorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A
Yin Z, You S, Zhang S, Zhang L, Wu B, Huang X, Lu S, Cao L, Zhang Y, Li D, Zhang X, Liu J, Sun Y, Zhang N. Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A. Biomedicine & Pharmacotherapy 2023, 166: 115228. PMID: 37557013, DOI: 10.1016/j.biopha.2023.115228.Peer-Reviewed Original ResearchConceptsMitochondrial pathway of apoptosisRegulate protein ubiquitinationPathway of apoptosisE3 ubiquitin ligaseVascular endothelial injuryDeath of vascular endothelial cellsEndothelial injuryMitochondrial pathwayUbiquitin ligaseWWP2 overexpressionProteasome pathwayProtein ubiquitinationBcl-2/BaxBiological processesWWP2Vascular endotheliumATP5ALipid-lowering drugsUbiquitinEffect of atorvastatinImproving vascular endothelial functionVascular endothelial functionDamaged vascular endotheliumVascular endothelial cellsMechanism of atorvastatinAn optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Zhou W, Li W, Wang S, Salovska B, Hu Z, Tao B, Di Y, Punyamurtula U, Turk B, Sessa W, Liu Y. An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells. Nature Communications 2023, 14: 3803. PMID: 37365174, PMCID: PMC10293293, DOI: 10.1038/s41467-023-39514-1.Peer-Reviewed Original ResearchConceptsPhosphorylation sitesSerine/threonine kinase AktMass spectrometry-based phosphoproteomicsThreonine kinase AktAkt-dependent phosphorylationAberrant Akt activationEndothelial cellsKinase substrateKinase AktCell signalingPhosphorylation profilePhenotypic outcomesDownstream signalingAkt activationAkt1 phosphorylationHuman diseasesSystem-level analysisAKT1Vascular endothelial cellsRich resourcePhosphorylationSignalingGrowth factorAktCellsEverolimus combined with PD-1 blockade inhibits progression of triple-negative breast cancer
Li G, Hu J, Cho C, Cui J, Li A, Ren P, Zhou J, Wei W, Zhang T, Liu X, Liu W. Everolimus combined with PD-1 blockade inhibits progression of triple-negative breast cancer. Cellular Signalling 2023, 109: 110729. PMID: 37257766, DOI: 10.1016/j.cellsig.2023.110729.Peer-Reviewed Original ResearchConceptsT cell tumor infiltrationTriple-negative breast cancerCD8+ T cell tumor infiltrationBreast cancerTumor infiltrationLack of target receptorsAnti-PD-1 antibodyAggressive subtype of breast cancerModels of triple-negative breast cancerSubtypes of breast cancerPD-L1 expressionEstrogen-positive breast cancerMTOR inhibitor everolimusPositive breast cancerProgression of triple-negative breast cancerReduced tumor growthAvailable treatment optionsCombination treatment strategiesPromote cancer cell survivalTreatment of estrogen-positive breast cancerAttenuate tumor progressionNonspecific cytotoxic agentsCancer cell survivalVascular endothelial cellsPotential therapeutic strategy
2022
Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications
Albert C, Bracaglia L, Koide A, DiRito J, Lysyy T, Harkins L, Edwards C, Richfield O, Grundler J, Zhou K, Denbaum E, Ketavarapu G, Hattori T, Perincheri S, Langford J, Feizi A, Haakinson D, Hosgood SA, Nicholson ML, Pober JS, Saltzman WM, Koide S, Tietjen GT. Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications. Nature Communications 2022, 13: 5998. PMID: 36220817, PMCID: PMC9553936, DOI: 10.1038/s41467-022-33490-8.Peer-Reviewed Original ResearchConceptsTargeted delivery applicationsTargeted nanoparticlesAntibody immobilizationAntigen-binding functionNanoparticlesNP surfaceDelivery applicationsRobust deliveryEndothelial cellsAmine couplingAntibody displayClinical translationIntracellular drug levelsVascular endothelial cellsCultured endothelial cellsNanomedicineDrug levelsVivo perfusionOrgan transplantsAdapterClinical settingHuman kidneyHuman settingImmobilizationEfficacyHigh Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells
Deng H, Schwartz MA. High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells. Journal Of The American Heart Association 2022, 11: e025337. PMID: 35861829, PMCID: PMC9707828, DOI: 10.1161/jaha.121.025337.Peer-Reviewed Original ResearchConceptsInflammatory cytokinesSmad2/3 activationEndothelial cellsNuclear translocationInflammatory cytokine treatmentGrowth factor betaVascular endothelial cellsQuantitative polymerase chain reactionSmad2/3 nuclear translocationTarget gene expressionBackground AtherosclerosisInflammatory mediatorsInflammatory pathwaysPolymerase chain reactionResult of inhibitionCytokine treatmentInhibits CytokineFactor betaMesenchymal transitionHigh fluid shear stressCytokinesEndMTGene expressionLaminar fluid shear stressFluid shear stressA mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells
Coon BG, Timalsina S, Astone M, Zhuang ZW, Fang J, Han J, Themen J, Chung M, Yang-Klingler YJ, Jain M, Hirschi KK, Yamamato A, Trudeau LE, Santoro M, Schwartz MA. A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells. Journal Of Cell Biology 2022, 221: e202109144. PMID: 35695893, PMCID: PMC9198948, DOI: 10.1083/jcb.202109144.Peer-Reviewed Original ResearchConceptsLaminar shear stressAnti-inflammatory transcription factorHigh laminar shear stressKruppel-like factor 2Vascular endothelial cellsSubsequent mechanistic investigationsArterial lesionsVascular inflammationDisturbed blood flowMyocardial infarctionVascular diseaseVascular remodelingBlood flowKLF2 expressionWhole-genome CRISPREndothelial cellsMajor causeBiomechanical factorsFactor 2Mitochondrial calciumMitochondrial metabolismKLF2InductionMetabolismMitochondrial pathway
2021
Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling
Budatha M, Zhang J, Schwartz MA. Fibronectin‐Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling. Journal Of The American Heart Association 2021, 10: e021160. PMID: 34472370, PMCID: PMC8649308, DOI: 10.1161/jaha.121.021160.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionPathological vascular remodelingVascular remodelingCarotid ligation modelPartial carotid ligation modelAortic constrictionInflammatory activationEndothelial cellsLigation modelArtery wall hypertrophyTransverse aortic constriction (TAC) modelHigh-fat dietIntegrin α5Aortic constriction modelWild-type miceBasement membranePartial carotid ligationVascular endothelial cellsProvisional matrix proteinsAcute atherosclerosisHyperlipidemic ApoEInflammatory markersLigation surgeryWall hypertrophyAcute model
2020
Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells
Azizi S, Azizi S. Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells. Journal Of NeuroVirology 2020, 26: 631-641. PMID: 32876900, PMCID: PMC7465881, DOI: 10.1007/s13365-020-00903-7.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2BetacoronavirusBrainBrain DiseasesBystander EffectCoronavirus InfectionsCOVID-19Epithelial CellsGene Expression RegulationHost-Pathogen InteractionsHumansLungNeuronsOlfaction DisordersPandemicsPeptidyl-Dipeptidase APneumonia, ViralPulmonary EmbolismSARS-CoV-2Signal TransductionSpike Glycoprotein, CoronavirusStrokeConceptsCOVID-19 patientsBystander injuryNeurological complicationsSARS-CoV-2Cerebral vascular endothelial cellsSecondary to hypoxiaInitial symptoms of COVID-19Post-COVID-19 patientsInflammatory neuromuscular diseasesVascular endothelial cellsImmunological abnormalitiesHost cellsSymptoms of COVID-19Oral cavityMetabolic abnormalitiesThrombo-EmbolismEpithelial/endothelial cellsInitial symptomsNeurological injuryEpithelial cellsFunctional receptorsPatientsPeripheral nervesMolecular mimicryEndothelial cells
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