2023
TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
Boutagy N, Fowler J, Grabinska K, Cardone R, Sun Q, Vazquez K, Whalen M, Zhu X, Chakraborty R, Martin K, Simons M, Romanoski C, Kibbey R, Sessa W. TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2218150120. PMID: 37695914, PMCID: PMC10515159, DOI: 10.1073/pnas.2218150120.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme ACytokinesEndothelial CellsHistonesHumansProtease LaTumor Necrosis Factor-alphaConceptsPyruvate dehydrogenase kinase 4Dehydrogenase kinase 4Lon proteasePyruvate dehydrogenase activityHistone acetylationMitochondrial metabolismKinase 4Specific gene lociPDH fluxEndothelial cellsSiRNA-mediated knockdownAcetyl-CoA generationLysine 27Gene transcriptionTCA fluxRNA sequencingHuman umbilical vein endothelial cellsProtein degradationHistone 3Gene locusUmbilical vein endothelial cellsNF-κB-dependent mechanismTricarboxylic acid cycle fluxVein endothelial cellsActive subunitSREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6
Fowler J, Boutagy N, Zhang R, Horikami D, Whalen M, Romanoski C, Sessa W. SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6. Journal Of Lipid Research 2023, 64: 100411. PMID: 37437844, PMCID: PMC10407908, DOI: 10.1016/j.jlr.2023.100411.Peer-Reviewed Original ResearchConceptsDirect transcriptional activationTranscriptional activationEndothelial cellsChemokine expressionChromatin immunoprecipitation sequencingCholesterol homeostasisSterol-responsive genesPro-inflammatory chemokinesLipid-lowering drugsAdaptive immune responsesPro-inflammatory genesTranscription factor SREBP2Endogenous cholesterol synthesisImmunoprecipitation sequencingResponsive genesMechanism of actionPromoter regionCardiovascular riskAtherosclerotic diseaseInflammatory phenotypeImmune modulationCardiovascular diseaseImmune responseInflammatory stimuliI interferonAn 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 ResearchMeSH KeywordsEndothelial CellsHumansOptogeneticsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktSignal TransductionConceptsPhosphorylation 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 factorAktCellsAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchMeSH KeywordsEndothelial CellsEndotheliumHumansSignal TransductionTransforming Growth Factor betaVascular DiseasesConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4
2022
Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells
Fowler JWM, Zhang R, Tao B, Boutagy NE, Sessa WC. Inflammatory stress signaling via NF-kB alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells. ELife 2022, 11: e79529. PMID: 35959888, PMCID: PMC9395194, DOI: 10.7554/elife.79529.Peer-Reviewed Original ResearchConceptsAcute inflammatory responseEndothelial cellsCholesterol homeostasisInflammatory stressInflammatory responsePro-inflammatory cytokinesSite of injuryCholesterol biosynthetic gene expressionNF-κB DNA bindingHuman endothelial cellsMultiple sclerosisInflammatory activationPrimary human endothelial cellsVascular endotheliumNF-κB-inducible genesTissue damageInducible targetAberrant activationRole of cholesterolSREBP2 activationMicrobial infectionsCholesterolKey transcription regulatorHomeostasisLeukocytes
2021
Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Park H, Furtado J, Poulet M, Chung M, Yun S, Lee S, Sessa WC, Franco CA, Schwartz MA, Eichmann A. Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. Circulation 2021, 144: 805-822. PMID: 34182767, PMCID: PMC8429266, DOI: 10.1161/circulationaha.120.053047.Peer-Reviewed Original ResearchConceptsActivin receptor-like kinase 1Hereditary hemorrhagic telangiectasiaHemorrhagic telangiectasiaVascular malformationsArteriovenous malformationsBlood flowGrowth factor receptor 2Endothelial growth factor receptor 2Vascular endothelial growth factor receptor 2Factor receptor 2Receptor-like kinase 1New potential targetsYAP/TAZ nuclear translocationDeficient miceTransmembrane serine-threonine kinase receptorsDevastating disorderAlk1 deletionReceptor 2Pharmacologic inhibitionCre linesPostnatal retinaMalformationsSerine-threonine kinase receptorsEndothelial cell migrationNuclear translocationCharacterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation
Bernatchez PN, Tao B, Bradshaw RA, Eveleth D, Sessa WC. Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation. Translational Vision Science & Technology 2021, 10: 21-21. PMID: 34111267, PMCID: PMC8132009, DOI: 10.1167/tvst.10.6.21.Peer-Reviewed Original ResearchMeSH KeywordsCapillary PermeabilityCaveolin 1Endothelial CellsHumansInflammationVascular Endothelial Growth Factor AConceptsOcular inflammationCell-permeable peptideRetinal damageVascular permeabilityModel of uveitisVascular endothelial growth factorNitric oxide releaseEndothelial growth factorNovel cell-permeable peptideEndothelial cell signalingVascular leakageClinical developmentInflammationOxide releaseEndothelial cellsNO releaseGrowth factorUveitisVEGFDistinct assaysPhage display technologyPresent studyVivoCell signalingPeptides
2015
Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report
Goodwin JE, Zhang X, Rotllan N, Feng Y, Zhou H, Fernández-Hernando C, Yu J, Sessa WC. Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2015, 35: 779-782. PMID: 25810297, PMCID: PMC4375730, DOI: 10.1161/atvbaha.114.304525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisBody WeightBrachiocephalic TrunkCholesterolDiet, High-FatDisease Models, AnimalEndothelial CellsGenotypeMacrophagesMice, Inbred C57BLMice, KnockoutPhenotypeReceptors, GlucocorticoidSeverity of Illness IndexTime FactorsTriglyceridesConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorHigh-fat diet feedingApoE knockout backgroundSevere atherosclerotic lesionsGroups of micePathogenesis of atherosclerosisAortic sinusTotal cholesterolAtherosclerosis progressionBrachiocephalic arteryControl miceInflammatory milieuTonic inhibitionDiet feedingMacrophage recruitmentAtherosclerotic lesionsBody weightMiceKnockout backgroundReceptorsLesionsAtherosclerosisInflammationArtery