2022
Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling
Canfrán-Duque A, Rotllan N, Zhang X, Andrés-Blasco I, Thompson B, Sun J, Price N, Fernández-Fuertes M, Fowler J, Gómez-Coronado D, Sessa W, Giannarelli C, Schneider R, Tellides G, McDonald J, Fernández-Hernando C, Suárez Y. Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling. Circulation 2022, 147: 388-408. PMID: 36416142, PMCID: PMC9892282, DOI: 10.1161/circulationaha.122.059062.Peer-Reviewed Original ResearchConceptsLipid-loaded macrophagesLineage-tracing mouse modelsSREBP transcriptional activityCholesterol biosynthetic intermediatesWestern diet feedingAccessible cholesterolDifferent macrophage populationsTranscriptomic analysisKey immune regulatorsPlasma membraneAtherosclerosis progressionImmune activationTranscriptional activityGene expressionDiet feedingInflammatory responseMouse bone marrowLiver X receptorBiosynthetic intermediatesSterol metabolismApoptosis susceptibilityToll-like receptor 4Proinflammatory gene expressionHuman coronary atherosclerotic lesionsMouse atherosclerotic plaquesMolecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes
Rodrigues MA, Gomes DA, Fiorotto R, Guerra MT, Weerachayaphorn J, Bo T, Sessa WC, Strazzabosco M, Nathanson MH. Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes. Hepatology Communications 2022, 6: 2748-2764. PMID: 35852334, PMCID: PMC9512452, DOI: 10.1002/hep4.2042.Peer-Reviewed Original ResearchConceptsLipid raftsCaveolin-1Intact lipid raftsType 3 inositol trisphosphate receptorApical regionC-terminal amino acidsTrisphosphate receptor type 3Madin-Darby canine kidney cellsCanine kidney cellsFluorescence microscopy techniquesInositol trisphosphate receptorApical localizationTrisphosphate receptorHeavy chain 9Molecular determinantsChemical disruptionAmino acidsITPR3RaftsKidney cellsIntracellular CaFinal common eventReceptor type 3Release channelMYH9
2021
The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice
Ribera J, Portolés I, Córdoba-Jover B, Rodríguez-Vita J, Casals G, González-de la Presa B, Graupera M, Solsona-Vilarrasa E, Garcia-Ruiz C, Fernández-Checa JC, Soria G, Tudela R, Esteve-Codina A, Espadas G, Sabidó E, Jiménez W, Sessa WC, Morales-Ruiz M. The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice. Communications Biology 2021, 4: 1192. PMID: 34654883, PMCID: PMC8519955, DOI: 10.1038/s42003-021-02722-w.Peer-Reviewed Original ResearchConceptsKey cellular processesIntracellular ATP productionCellular processesZebrafish embryosDownstream substratesATP biosynthesisProteome analysisMitochondrial membraneEndothelial cellsDHX15ATP productionRegulatory functionsDifferential expressionComplex IVascular regulatory functionEnergy metabolismVascular biologyTumor metastasisTherapeutical targetGene deficiencyPrimary tumor growthLower oxygen consumptionVascular physiologyDownregulation of VEGFCellsDefective 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 translocationEruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation
Cabodevilla AG, Tang S, Lee S, Mullick AE, Aleman JO, Hussain MM, Sessa WC, Abumrad NA, Goldberg IJ. Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation. Journal Of Clinical Investigation 2021, 131: e145800. PMID: 34128469, PMCID: PMC8203467, DOI: 10.1172/jci145800.Peer-Reviewed Original ResearchConceptsLPL-deficient miceScavenger receptor BISkin macrophagesEruptive xanthomasStudy of patientsLipid droplet biogenesisAccumulation of triglyceridesEndothelial cell barrierLipoprotein lipase hydrolysisChylomicron uptakeDroplet biogenesisReceptor BITG accumulationTissue uptakeTriglyceride accumulationDietary lipidsChylomicronsEndothelial cellsLipid accumulationAortic ECsLipid dropletsMacrophagesTriglyceridesHyperchylomicronemic patientsCultured ECs
2010
Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice
Kreiger M, Di Lorenzo A, Teutsch C, Kauser K, Sessa WC. Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice. Laboratory Investigation 2010, 90: 1573-1581. PMID: 20585312, PMCID: PMC3248785, DOI: 10.1038/labinvest.2010.116.Peer-Reviewed Original ResearchConceptsCav-1 KO miceAngiotensin receptor blockersKO miceCardiac functionLV hypertrophyWT miceCardiac hypertrophyΒ-myosin heavy chainBody weight ratioTibial length ratioNatriuretic peptide ACaveolin-1-deficient miceCav-1 KOReceptor blockersPerivascular fibrosisVentricular hypertrophyVentricular weightAngiotensin IIIntramyocardial vesselsSpontaneous modelUnique genetic modelHypertrophyMiceTreatmentCaveolin-1
2004
Antiangiogenic therapy Creating a unique “window” of opportunity
Lin M, Sessa W. Antiangiogenic therapy Creating a unique “window” of opportunity. Cancer Cell 2004, 6: 529-531. PMID: 15607955, DOI: 10.1016/j.ccr.2004.12.003.Peer-Reviewed Original ResearchAngiogenesis InhibitorsAngiopoietin-1AnimalsAntibodies, MonoclonalBasement MembraneBlood VesselsCell MovementCollagenasesCombined Modality TherapyGamma RaysGliomaHumansMiceModels, BiologicalNeoplasmsNeovascularization, PathologicPericytesReceptor, TIE-2Time FactorsVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor Assays
2000
In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation
Bucci M, Gratton J, Rudic R, Acevedo L, Roviezzo F, Cirino G, Sessa W. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nature Medicine 2000, 6: 1362-1367. PMID: 11100121, DOI: 10.1038/82176.Peer-Reviewed Original ResearchConceptsCaveolin-1Signal transductionSmall-molecule mimicryCaveolae assemblyInternalization sequenceCoat proteinEndothelial cellsPhysiological importanceEndothelial nitric oxide synthase (eNOS) inhibitorTransductionCholesterol transportNitric oxide synthase inhibitorChimeric peptideInhibits nitric oxide synthesisOxide synthase inhibitorNitric oxide synthesisNew therapeutic approachesNitric oxide productionSelective inhibitionDomainPeptidesCaveolinAcute inflammationCellsSystemic administrationGeldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo
Bucci M, Roviezzo F, Cicala C, Sessa W, Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo. British Journal Of Pharmacology 2000, 131: 13-16. PMID: 10960063, PMCID: PMC1572305, DOI: 10.1038/sj.bjp.0703549.Peer-Reviewed Original ResearchConceptsAnti-inflammatory effectsAnti-inflammatory actionEdema formationRU 486Heat shock protein 90Shock protein 90Endothelial nitric oxide synthaseEndothelium-dependent relaxationAnti-inflammatory dosePotential anti-inflammatory drugsVascular endothelial growth factorNitric oxide synthaseAnti-inflammatory drugsEndothelial growth factorDose-dependent mannerProtein 90Specific inhibitorIntact blood vesselsIntraplantar administrationPaw edemaMiddle arteryOxide synthaseRat aortaTherapeutic rationaleGlucocorticoid receptorAcute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo
Luo Z, Fujio Y, Kureishi Y, Rudic R, Daumerie G, Fulton D, Sessa W, Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide–dependent vasomotor activity in vivo. Journal Of Clinical Investigation 2000, 106: 493-499. PMID: 10953024, PMCID: PMC380252, DOI: 10.1172/jci9419.Peer-Reviewed Original ResearchConceptsDN-AktEndothelial cell nitric oxide synthaseMyr-AktSerine/threonine protein kinase AktProtein kinase AktDominant-negative AktNitric oxideVasomotor toneFemoral arteryAkt functionReplication-defective adenoviral constructKinase AktActive AktEndothelium-dependent vasodilatationKey regulatorEndothelium-independent vasodilatorEndothelium-dependent vasomotionRabbit femoral artery modelNitric oxide synthaseAorta ex vivoImportant regulatorGene transferDoppler flow measurementsAktENOS inhibitorTemporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice
Rudic R, Bucci M, Fulton D, Segal S, Sessa W. Temporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice. Circulation Research 2000, 86: 1160-1166. PMID: 10850968, DOI: 10.1161/01.res.86.11.1160.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarotid Artery, CommonCell DeathDrug CombinationsIn Vitro TechniquesMaleMiceMice, Inbred C57BLMuscle, Smooth, VascularNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRegional Blood FlowTime FactorsTunica MediaVasodilator AgentsVasomotor SystemConceptsLeft common carotid arteryRight common carotid arteryCommon carotid arteryCarotid arteryBlood flowLeft external carotid arteryEndothelial NO synthase (eNOS) functionEndothelial NO synthase (eNOS) mRNAExternal carotid arteryNO synthase mRNANitrovasodilator sodium nitroprussideAcute ligationEndothelial dysfunctionArterial remodelingControl arteriesVascular remodelingAdult miceSodium nitroprussideDay 7Structural remodelingArteryLuminal remodelingMarked reductionProtein levelsMiceVasomotor control in arterioles of the mouse cremaster muscle
HUNGERFORD J, SESSA W, SEGAL S. Vasomotor control in arterioles of the mouse cremaster muscle. The FASEB Journal 2000, 14: 197-207. PMID: 10627294, DOI: 10.1096/fasebj.14.1.197.Peer-Reviewed Original ResearchConceptsMouse cremaster muscleVasomotor controlCremaster musclePerivascular sympathetic nerve stimulationAnesthetized C57Bl6 miceMicroiontophoresis of acetylcholineSympathetic nerve stimulationNitro-L-arginineConcentration-dependent vasoconstrictionBlood flow controlCremaster muscle preparationFocal vasoconstrictionVasodilatory responseNerve stimulationTransgenic mouse technologyVasomotor responsesC57BL6 miceCardiovascular functionNormal miceMuscle preparationsArteriolesBiphasic responseIntravital microscopyAcetylcholineVasoconstriction
1999
Molecular control of nitric oxide synthases in the cardiovascular system
Papapetropoulos A, Rudic R, Sessa W. Molecular control of nitric oxide synthases in the cardiovascular system. Cardiovascular Research 1999, 43: 509-520. PMID: 10690323, DOI: 10.1016/s0008-6363(99)00161-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCardiovascular DiseasesCardiovascular SystemCentral Nervous SystemGene Expression RegulationHomeostasisHumansImmune SystemMiceMice, KnockoutNeovascularization, PathologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRatsVasomotor SystemA vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase
Guillot P, Guan J, Liu L, Kuivenhoven J, Rosenberg R, Sessa W, Aird W. A vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase. Journal Of Clinical Investigation 1999, 103: 799-805. PMID: 10079100, PMCID: PMC408151, DOI: 10.1172/jci6017.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthase geneEndothelial nitric oxide synthaseMurine endothelial progenitor cellsGrowth factor antibodyNitric oxide synthase geneNitric oxide synthaseEndothelial progenitor cellsOxide synthase geneFactor antibodyOxide synthaseVascular bedResponse elementCardiac expressionTransgenic micePDGF-ABCardiac endotheliumEno expressionCardiac myocytesSkeletal muscleProgenitor cellsSkeletal myocytesEndotheliumMiceBrainBeta-galactosidase activityNitric Oxide in Endothelial Dysfunction and Vascular Remodeling: Clinical Correlates and Experimental Links
Rudic R, Sessa W. Nitric Oxide in Endothelial Dysfunction and Vascular Remodeling: Clinical Correlates and Experimental Links. American Journal Of Human Genetics 1999, 64: 673-677. PMID: 10052999, PMCID: PMC1377782, DOI: 10.1086/302304.Peer-Reviewed Original Research
1997
The First 35 Amino Acids and Fatty Acylation Sites Determine the Molecular Targeting of Endothelial Nitric Oxide Synthase into the Golgi Region of Cells: A Green Fluorescent Protein Study
Liu J, Hughes T, Sessa W. The First 35 Amino Acids and Fatty Acylation Sites Determine the Molecular Targeting of Endothelial Nitric Oxide Synthase into the Golgi Region of Cells: A Green Fluorescent Protein Study. Journal Of Cell Biology 1997, 137: 1525-1535. PMID: 9199168, PMCID: PMC2137822, DOI: 10.1083/jcb.137.7.1525.Peer-Reviewed Original ResearchConceptsPalmitoylation-deficient mutantN-myristoylationNIH 3T3 cellsMembrane associationGolgi regionPalmitoylation sitesAmino acidsGreen fluorescent protein studiesGolgi complexFatty acylation sitesGFP fusion proteinBiochemical studiesFluorescent protein chimerasDiffuse fluorescence patternEndothelial cellsEndothelial nitric oxide synthaseCytosolic natureGFP tagFatty acylationAcylated proteinsGolgi markersProtein chimerasIntracellular membranesAcylation siteIntracellular targeting
1996
Elevated blood pressures in mice lacking endothelial nitric oxide synthase
Shesely E, Maeda N, Kim H, Desai K, Krege J, Laubach V, Sherman P, Sessa W, Smithies O. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 13176-13181. PMID: 8917564, PMCID: PMC24066, DOI: 10.1073/pnas.93.23.13176.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBlood PressureCattleChimeraDNA PrimersEndothelium, VascularFemaleGenotypeHeterozygoteHypertensionIsoenzymesKidneyLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutNitric Oxide SynthasePolymerase Chain ReactionReninRNA, MessengerStem CellsTranscription, GeneticConceptsEndothelial nitric oxide synthaseBlood pressureNitric oxide synthaseHeart rateENOS proteinOxide synthaseENOS mutant miceLipopolysaccharide-induced deathElevated blood pressureNormal blood pressurePlasma renin concentrationBlood pressure regulationLower body weightKidney renin mRNAAnti-eNOS antibodiesAppropriate genetic controlsENOS locusENOS genotypesRenin concentrationVascular toneFemale miceRenin mRNAENOS geneENOS mutationBody weight