2021
Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis
Zhang X, Sun J, Canfrán-Duque A, Aryal B, Tellides G, Chang YJ, Suárez Y, Osborne TF, Fernández-Hernando C. Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis. JCI Insight 2021, 6: e147984. PMID: 34003795, PMCID: PMC8262461, DOI: 10.1172/jci.insight.147984.Peer-Reviewed Original ResearchConceptsHematopoietic cellsHistone methylation/acetylationSingle-cell RNA-seq analysisMethylation/acetylationHistone H3 Lys9RNA-seq analysisProgression of atherosclerosisEpigenetic marksLysine methyltransferasesH3 Lys9Epigenetic modificationsDNA methylationNoncoding RNAsCell regulatorsSETDB2Vascular inflammationAtherosclerotic lesionsAtherosclerotic plaquesMyeloid cell recruitmentGenetic deletionLDLR knockout miceEnhanced expressionHepatic lipid metabolismMurine atherosclerotic lesionsGenes
2019
Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation
Ramírez CM, Zhang X, Bandyopadhyay C, Rotllan N, Sugiyama MG, Aryal B, Liu X, He S, Kraehling JR, Ulrich V, Lin CS, Velazquez H, Lasunción MA, Li G, Suárez Y, Tellides G, Swirski FK, Lee WL, Schwartz MA, Sessa WC, Fernández-Hernando C. Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation. Circulation 2019, 140: 225-239. PMID: 31154825, PMCID: PMC6778687, DOI: 10.1161/circulationaha.118.038571.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseDiet-induced atherosclerosisNO productionVascular inflammationENOS activationEndothelial nitric oxide synthase activationNitric oxide synthase activationAthero-protective functionsLipid metabolic factorsEndothelial cell inflammationNitric oxide synthaseWild-type miceMice Lacking ExpressionProduction of NOExtracellular matrix remodelingInflammatory primingHyperlipidemic miceInflammatory pathwaysAortic archCell inflammationOxide synthaseMetabolic factorsMouse modelAtherosclerosisInflammation
2017
Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis
Price NL, Rotllan N, Canfrán-Duque A, Zhang X, Pati P, Arias N, Moen J, Mayr M, Ford DA, Baldán Á, Suárez Y, Fernández-Hernando C. Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis. Cell Reports 2017, 21: 1317-1330. PMID: 29091769, PMCID: PMC5687841, DOI: 10.1016/j.celrep.2017.10.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisATP Binding Cassette Transporter 1Blood GlucoseCells, CulturedCholesterolCholesterol, HDLDisease ProgressionGene Regulatory NetworksMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMitochondrial Trifunctional Protein, beta SubunitMyocardiumReceptors, LDLConceptsPlaque burdenMiR-33MiR-33-deficient miceReduced plaque burdenProgression of atherosclerosisPro-atherogenic effectsMacrophage cholesterol effluxDecreases lipid accumulationTreatment of atherosclerosisMacrophage-specific lossMiR-33 deficiencyPromotes obesityHDL levelsInsulin resistancePlaque macrophagesProtective effectHyperlipidemic conditionsCholesterol effluxPlaque developmentLipid metabolismAtherosclerosisLipid accumulationHDL biogenesisPromising targetMacrophages
2014
Improved repair of dermal wounds in mice lacking microRNA‐155
van Solingen C, Araldi E, Chamorro‐Jorganes A, Fernández‐Hernando C, Suárez Y. Improved repair of dermal wounds in mice lacking microRNA‐155. Journal Of Cellular And Molecular Medicine 2014, 18: 1104-1112. PMID: 24636235, PMCID: PMC4112003, DOI: 10.1111/jcmm.12255.Peer-Reviewed Original ResearchConceptsMiR-155Wound tissueWound healingIncreased expressionWound closureImpaired wound repairAnalysis of woundsSkin of miceMiR-155 targetsType 1 collagenWild-type animalsInflammatory mediatorsWT miceWound healing processImmune responseInterleukin-4Healthy skinMicroRNA-155Punch woundsMiceElevated numbersBeneficial effectsWound closingDermal wound healingDermal woundsAutoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells
Chamorro-Jorganes A, Araldi E, Rotllan N, Cirera-Salinas D, Suárez Y. Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells. Journal Of Cell Science 2014, 127: 1169-1178. PMID: 24463821, PMCID: PMC3953812, DOI: 10.1242/jcs.130518.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Lewis LungCells, CulturedFibroblast Growth Factor 2Gene ExpressionGlypicansHuman Umbilical Vein Endothelial CellsHumansMaleMiceMicroRNAsNeoplasm TransplantationNeovascularization, PathologicNeovascularization, PhysiologicReceptor, Fibroblast Growth Factor, Type 1RNA InterferenceSignal Transduction
2011
MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1
Chamorro-Jorganes A, Araldi E, Penalva LO, Sandhu D, Fernández-Hernando C, Suárez Y. MicroRNA-16 and MicroRNA-424 Regulate Cell-Autonomous Angiogenic Functions in Endothelial Cells via Targeting Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2595-2606. PMID: 21885851, PMCID: PMC3226744, DOI: 10.1161/atvbaha.111.236521.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAnimalsCattleCell MovementCell ProliferationCells, CulturedEndothelium, VascularHumansMiceMice, SCIDMicroRNAsNeovascularization, PhysiologicReceptor, Fibroblast Growth Factor, Type 1Signal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVEGF receptor 2MiR-424 overexpressionPosttranscriptional regulationGrowth factor receptor 1MiR-424Factor receptor 1MiR-16Vascular endothelial growth factorFibroblast growth factor receptor 1Endothelial cellsMature miR-16Basic fibroblast growth factor (bFGF) treatmentFibroblast growth factor treatmentGrowth factorCellular processesBioinformatics approachPrimary transcriptAbility of ECsDownstream componentsTarget genesVascular endothelial growth factor receptor 2Receptor 1Endothelial growth factor receptor 2Cord formationLentiviral overexpression
2010
MicroRNAs Are Necessary for Vascular Smooth Muscle Growth, Differentiation, and Function
Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC. MicroRNAs Are Necessary for Vascular Smooth Muscle Growth, Differentiation, and Function. Arteriosclerosis Thrombosis And Vascular Biology 2010, 30: 1118-1126. PMID: 20378849, PMCID: PMC2880481, DOI: 10.1161/atvbaha.109.200873.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAortaCell DifferentiationCell ProliferationCells, CulturedDEAD-box RNA HelicasesEmbryo LossEndoribonucleasesGene Expression Regulation, DevelopmentalGenotypeGestational AgeHemorrhageIntegrasesLiver DiseasesMaleMiceMice, KnockoutMicrofilament ProteinsMicroRNAsMuscle DevelopmentMuscle ProteinsMuscle, Smooth, VascularNuclear ProteinsPhenotypeRibonuclease IIIStress FibersTrans-ActivatorsTranscriptional ActivationTransfectionUmbilical ArteriesVasoconstrictionVasodilationConceptsLate embryonic lethalityFundamental cellular processesContractile differentiationContractile protein markersDicer-dependent miRNAsActin stress fibersDeletion of DicerRole of miRNAsDicer resultsOverexpression of microRNAEmbryonic lethalityMiRNA synthesisCellular processesRate-limiting enzymeStress fibersVascular developmentMuscle growthCell typesCellular proliferationMiRNAsVascular smooth muscle growthVascular smooth muscle proliferationMicroRNAsProtein markersDicer
2009
Cutting Edge: TNF-Induced MicroRNAs Regulate TNF-Induced Expression of E-Selectin and Intercellular Adhesion Molecule-1 on Human Endothelial Cells: Feedback Control of Inflammation
Suárez Y, Wang C, Manes TD, Pober JS. Cutting Edge: TNF-Induced MicroRNAs Regulate TNF-Induced Expression of E-Selectin and Intercellular Adhesion Molecule-1 on Human Endothelial Cells: Feedback Control of Inflammation. The Journal Of Immunology 2009, 184: 21-25. PMID: 19949084, PMCID: PMC2797568, DOI: 10.4049/jimmunol.0902369.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedEndothelial CellsE-SelectinFeedback, PhysiologicalGene ExpressionGene Expression RegulationHumansImmunohistochemistryInflammationIntercellular Adhesion Molecule-1MicroRNAsOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionTransfectionTumor Necrosis Factor-alphaConceptsEndothelial cellsGene expressionUntranslated regionHuman endothelial cellsMiRNAsCultured endothelial cellsTarget sequenceMicroRNA pairsNegative feedback controlMiR-31Adhesion moleculesCellsExpressionNeutrophil adhesionE-selectinAdhesion molecule-1AdhesionTransfectionIntercellular adhesion molecule-1MRNAMolecule-1SequenceEndothelial adhesion moleculesSpecific antagonismICAM-1
2008
Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence
Schleicher M, Shepherd BR, Suarez Y, Fernandez-Hernando C, Yu J, Pan Y, Acevedo LM, Shadel GS, Sessa WC. Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence. Journal Of Cell Biology 2008, 180: 101-112. PMID: 18195103, PMCID: PMC2213620, DOI: 10.1083/jcb.200706072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCells, CulturedCellular SenescenceCytoskeletonElectron Transport Complex IEndothelial CellsEndothelium, VascularHumansMiceMice, Inbred StrainsMitochondriaMitochondrial MembranesNeovascularization, PhysiologicNeuropeptidesPhosphatidylinositol 3-KinasesProhibitinsProto-Oncogene Proteins c-aktRac GTP-Binding ProteinsRac1 GTP-Binding ProteinReactive Oxygen SpeciesRepressor ProteinsSignal TransductionConceptsProhibitin 1Mitochondrial functionKnockdown of PHB1Inner mitochondrial membraneEndothelial cell motilityEndothelial cellsCytoskeletal rearrangementsMitochondrial membraneVivo angiogenesis assaysCell motilityAngiogenic capacityCellular senescenceReactive oxygen speciesMitochondrial productionFunctional blood vesselsImportant regulatorSenescenceAngiogenesis assayTube formationOxygen speciesVascular homeostasisCellsVascular systemRac1Yeast
2007
Alloimmunity to Human Endothelial Cells Derived from Cord Blood Progenitors
Suárez Y, Shepherd BR, Rao DA, Pober JS. Alloimmunity to Human Endothelial Cells Derived from Cord Blood Progenitors. The Journal Of Immunology 2007, 179: 7488-7496. PMID: 18025193, DOI: 10.4049/jimmunol.179.11.7488.Peer-Reviewed Original ResearchConceptsCell-derived endothelial cellsEndothelial progenitor cellsCord blood endothelial progenitor cellsBlood endothelial progenitor cellsEndothelial cellsCord blood progenitorsExpression of proteinsMemory T cell responsesHuman endothelial cellsT cell responsesProgenitor cellsBlood progenitorsOrgan repairRegenerative medicineAllogeneic responseAdhesion moleculesTissue engineeringTissue sourcesMHC moleculesCell responsesSuch cellsCellsSame donorAlloimmunityVitroDicer Dependent MicroRNAs Regulate Gene Expression and Functions in Human Endothelial Cells
Suárez Y, Fernández-Hernando C, Pober JS, Sessa WC. Dicer Dependent MicroRNAs Regulate Gene Expression and Functions in Human Endothelial Cells. Circulation Research 2007, 100: 1164-1173. PMID: 17379831, DOI: 10.1161/01.res.0000265065.26744.17.Peer-Reviewed Original ResearchConceptsGene expressionHuman endothelial cellsEndogenous miRNA levelsImportance of miRNAsMaturation of microRNAsEC gene expressionEndothelial cellsTek/TieKnockdown of DicerDICER-dependent microRNAsRole of DicerMiRNA expression profilesKDR/VEGFR2MiR-222/221Dicer knockdownDependent microRNAsSynthase protein levelsDicerKey regulatorExpression profilesKey enzymePhysiological pathwaysCord formationEndothelial biologyMiRNAs
2002
AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*
Cuadrado A, Garcı́a-Fernández L, González L, Suárez Y, Losada A, Alcaide V, Martı́nez T, Fernández-Sousa J, Sánchez-Puelles J, Muñoz A. AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*. Journal Of Biological Chemistry 2002, 278: 241-250. PMID: 12414812, DOI: 10.1074/jbc.m201010200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCell DivisionCell SurvivalCells, CulturedDepsipeptidesEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFemaleFibroblastsFlow CytometryGlutathioneHumansJNK Mitogen-Activated Protein KinasesKidney NeoplasmsMiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPeptides, CyclicPhosphorylationProto-Oncogene Proteins pp60(c-src)Receptors, Platelet-Derived Growth FactorTumor Cells, CulturedConceptsEpidermal growth factor receptorP38 MAPK activationP38 MAPKNon-receptor protein tyrosine kinase SrcGrowth factor receptorMAPK activationProtein tyrosine kinase SrcStress response programSustained activationFactor receptorCancer cellsMDA-MB-231 breast cancer cellsHuman cancer cellsBenzyloxycarbonyl-VADKinase SrcHuman MDA-MB-231 breast cancer cellsMDA-MB-231 cellsMolecular basisKinase JNKPretreatment of cellsMouse embryosEGFR activationFluoromethyl ketoneGrowth arrestHuman renal cancer
1998
Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL
Calvo D, Gómez-Coronado D, Suárez Y, Lasunción M, Vega M. Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL. Journal Of Lipid Research 1998, 39: 777-788. PMID: 9555943, DOI: 10.1016/s0022-2275(20)32566-9.Peer-Reviewed Original ResearchConceptsHigh-affinity receptorHuman CD36Lipoprotein HDLAffinity receptorPathogenesis of atherosclerosisLow-density lipoproteinFoam cell formationBinding of lipoproteinsFatty acid metabolismSR-BIActive fatty acid metabolismDensity lipoproteinModified lipoproteinsScavenger receptorsLipid metabolismCD36CLA-1Monoclonal antibodiesLDLLipoproteinHDLAcid metabolismReceptorsVLDLNative lipoproteins