2024
Abstract 129: Hypercholesterolemia-induced Lxr Signaling In Smc Contributes To Atherosclerotic Lesion Remodeling And Regulates Vascular And Visceral Smc Function
Zhang H, Biwer L, Saenz de Urturi D, Fernandez-Tussy P, Jovin D, Huang Y, Zhang X, Esplugues E, Greif D, Suarez Y, Fernandez-Hernando C. Abstract 129: Hypercholesterolemia-induced Lxr Signaling In Smc Contributes To Atherosclerotic Lesion Remodeling And Regulates Vascular And Visceral Smc Function. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44 DOI: 10.1161/atvb.44.suppl_1.129.Peer-Reviewed Original ResearchLiver X receptorTranscription factorsVascular smooth muscle cellsRegulation of lipid metabolismLXR signalingB geneScRNA-seqFate decisionsSignaling eventsSMC functionGene expressionActivation of liver X receptorCell statesLesion remodelingCharacterized miceLipid metabolismLineage tracingPhenotypic switchingX receptorReduced fibrous cap thicknessTranscriptionFeatures of plaque instabilitySmooth muscle cellsLipid absorptionProgression of atherosclerosis
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 plaquesTargeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression
Zhang X, Rotllan N, Canfrán-Duque A, Sun J, Toczek J, Moshnikova A, Malik S, Price NL, Araldi E, Zhong W, Sadeghi MM, Andreev OA, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C. Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression. Circulation Research 2022, 131: 77-90. PMID: 35534923, PMCID: PMC9640270, DOI: 10.1161/circresaha.121.320296.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionNature of miRNAsSingle-cell RNA sequencing analysisSingle-cell RNA transcriptomicsAnti-miRNA technologiesRNA sequencing analysisExpression of miRNAsRNA transcriptomicsNew therapeutic opportunitiesEntire pathwayMiRNA therapeuticsAtherosclerotic plaque macrophagesHuman diseasesMiRNAsSequencing analysisSpecific tissuesMetabolic tissuesTargeted suppressionMiR-33 inhibitionProtective miRNAsNumerous diseasesPharmacological inhibitionLipid accumulationTarget effects
2021
MMAB promotes negative feedback control of cholesterol homeostasis
Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCell Line, TumorCholesterolCholesterol, LDLFeedback, PhysiologicalGene Expression ProfilingHeLa CellsHep G2 CellsHomeostasisHumansHydroxymethylglutaryl CoA ReductasesLiverMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticReceptors, LDLRNA InterferenceSterol Regulatory Element Binding Protein 2ConceptsCholesterol biosynthesisCholesterol homeostasisMouse hepatic cell lineIntegrative genomic strategyIntricate regulatory networkMaster transcriptional regulatorCellular cholesterol levelsHMGCR activityLDL-cholesterol uptakeCholesterol levelsHuman hepatic cellsSterol contentGenomic strategiesTranscriptional regulatorsRegulatory networksIntracellular cholesterol levelsGene expressionUnexpected roleHepatic cell linesBiosynthesisMMABIntracellular levelsCell linesHomeostasisExpression of SREBP2MicroRNA regulation of cholesterol metabolism
Citrin KM, Fernández‐Hernando C, Suárez Y. MicroRNA regulation of cholesterol metabolism. Annals Of The New York Academy Of Sciences 2021, 1495: 55-77. PMID: 33521946, PMCID: PMC8938903, DOI: 10.1111/nyas.14566.Peer-Reviewed Original ResearchConceptsDifferent cell typesCell typesMultiple mRNA targetsCholesterol homeostasisSmall noncoding RNAsMicroRNA activityCholesterol-laden cellsMicroRNA regulationCholesterol metabolismMRNA targetsNoncoding RNAsPosttranscriptional levelGene expressionSpecialized functionsMicroRNAsCurrent knowledgeTarget interactionsHomeostasisMetabolismPathwayExpressionMultiple stagesRNARegulationDistinctive effects
2018
Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis
Aryal B, Suárez Y. Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis. Vascular Pharmacology 2018, 114: 64-75. PMID: 29551552, PMCID: PMC6177333, DOI: 10.1016/j.vph.2018.03.001.Peer-Reviewed Original ResearchConceptsNon-coding RNAsNon-coding RNA regulationSmall non-coding RNAsMultiple cell functionsRNA regulationMacrophage functionRNA moleculesGene expressionPotential regulatorKey playersVascular biologyPathogenesis of atherosclerosisCell functionSpecific roleLncRNAsRegulationRNAMechanism of actionEndothelial cellsInitial eventVascular integrityRecruitment of monocytesMicroRNAsDevelopment of atherosclerosisBiology
2017
Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages
Araldi E, Fernández-Fuertes M, Canfrán-Duque A, Tang W, Cline GW, Madrigal-Matute J, Pober JS, Lasunción MA, Wu D, Fernández-Hernando C, Suárez Y. Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages. Cell Reports 2017, 19: 2743-2755. PMID: 28658622, PMCID: PMC5553565, DOI: 10.1016/j.celrep.2017.05.093.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Activator of transcriptionCholesterol biosynthetic pathwayTranscriptional repressionBiosynthetic pathwayLanosterol accumulationGene productsSterol intermediatesSignal transducerGene expressionSelective regulatorSTAT2 activationInnate immune responseType I interferonConditional disruptionCritical functionsMembrane fluidityROS productionMacrophage immunityListeria monocytogenes infectionResistance of miceMouse macrophagesInnate immunityI interferonCYP51A1
2016
ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression
Aryal B, Rotllan N, Araldi E, Ramírez CM, He S, Chousterman BG, Fenn AM, Wanschel A, Madrigal-Matute J, Warrier N, Martín-Ventura JL, Swirski FK, Suárez Y, Fernández-Hernando C. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature Communications 2016, 7: 12313. PMID: 27460411, PMCID: PMC4974469, DOI: 10.1038/ncomms12313.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-Like Protein 4AnimalsApoptosisAtherosclerosisBone Marrow TransplantationCell ProliferationCell SurvivalDisease ProgressionFoam CellsHematopoietic Stem CellsHumansInflammationLeukocytosisMacrophagesMaleMiceMice, Inbred C57BLModels, BiologicalMonocytesMyeloid Progenitor CellsPlaque, AtheroscleroticConceptsFoam cell formationMyeloid progenitor cell expansionANGPTL4 deficiencyCell formationMacrophage gene expressionLipid raft contentMyeloid progenitor populationsProgenitor cell expansionUpregulated genesProgenitor populationsGene expressionHaematopoietic cellsCell surfaceMacrophage apoptosisCell expansionCells resultsProtein 4Lipid accumulationCD36 expressionLike protein 4ExpressionProfound effectMacrophagesGenesLarger atherosclerotic plaques
2015
The miR-199–dynamin regulatory axis controls receptor-mediated endocytosis
Aranda JF, Canfrán-Duque A, Goedeke L, Suárez Y, Fernández-Hernando C. The miR-199–dynamin regulatory axis controls receptor-mediated endocytosis. Journal Of Cell Science 2015, 128: 3197-3209. PMID: 26163491, PMCID: PMC4582188, DOI: 10.1242/jcs.165233.Peer-Reviewed Original ResearchConceptsClathrin heavy chainReceptor-mediated endocytosisIntracellular traffickingLow-density lipoprotein receptorGene expressionMiR-199aSmall non-coding RNAsNon-coding RNAsTarget gene expressionDynamin genesEukaryotic cellsHuman cell linesEndocytic transportGTPase familyCav-1 expressionUnexpected layerCaveolin-1Intronic sequencesIntracellular transportPhysiological processesEndocytosisImportant regulatorMiR-199bCell linesGenes
2013
MicroRNA 33 Regulates Glucose Metabolism
Ramírez CM, Goedeke L, Rotllan N, Yoon JH, Cirera-Salinas D, Mattison JA, Suárez Y, de Cabo R, Gorospe M, Fernández-Hernando C. MicroRNA 33 Regulates Glucose Metabolism. Molecular And Cellular Biology 2013, 33: 2891-2902. PMID: 23716591, PMCID: PMC3719675, DOI: 10.1128/mcb.00016-13.Peer-Reviewed Original ResearchConceptsHost genesSterol regulatory element-binding protein (SREBP) genesSmall noncoding RNAsKey regulatory enzymeMiR-33bIntronic miRNAsHuman hepatic cellsMiR-33a/bPosttranscriptional regulationRegulatory genesExpression of PCK1Regulation of lipidNoncoding RNAsProtein geneG6pc expressionGene expressionBiological processesRegulatory enzymeMicroRNA-33GenesSpecific pathwaysMetabolic diseasesNovel therapeutic targetPhosphoenolpyruvate carboxykinaseRecent discoveryA Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression
Goedeke L, Vales-Lara FM, Fenstermaker M, Cirera-Salinas D, Chamorro-Jorganes A, Ramírez CM, Mattison JA, de Cabo R, Suárez Y, Fernández-Hernando C. A Regulatory Role for MicroRNA 33* in Controlling Lipid Metabolism Gene Expression. Molecular And Cellular Biology 2013, 33: 2339-2352. PMID: 23547260, PMCID: PMC3648071, DOI: 10.1128/mcb.01714-12.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionRegulatory roleTarget gene networkKey transcriptional regulatorTarget gene expressionMetabolism gene expressionIntronic microRNAsHuman hepatic cellsLipid metabolismSterol regulatory element-binding protein 2Transcriptional regulatorsSister strandsGene networksLipid metabolism gene expressionSteady-state levelsHost genesFatty acid metabolismFatty acid oxidationKey enzymeLipid homeostasisPassenger strandMicroRNA-33Functional roleProtein 2MicroRNAs as pharmacological targets in endothelial cell function and dysfunction
Chamorro-Jorganes A, Araldi E, Suárez Y. MicroRNAs as pharmacological targets in endothelial cell function and dysfunction. Pharmacological Research 2013, 75: 15-27. PMID: 23603154, PMCID: PMC3752325, DOI: 10.1016/j.phrs.2013.04.002.Peer-Reviewed Original ResearchConceptsEndothelial cell functionShort non-coding RNAsCell functionPost-transcriptional levelNon-coding RNAsEndothelial-specific microRNAsGene expressionMorphogenic capacityCritical regulatorNormal endothelial cell functionMicroRNAsCell dysfunctionEndothelial cell dysfunctionPathophysiological conditionsLatest insightsParacrine mannerPharmacological targetsEndothelial cellsTherapeutic potentialBarrier functionTraffickingRNALeukocyte traffickingRegulatorTarget
2012
miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish
Stahlhut C, Suárez Y, Lu J, Mishima Y, Giraldez AJ. miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish. Development 2012, 139: 4356-4365. PMID: 23132244, PMCID: PMC3509730, DOI: 10.1242/dev.083774.Peer-Reviewed Original ResearchConceptsMiR-1/206Post-transcriptional modulatorsMiRNA-target interactionsMiR-1Appropriate physiological responsesRegulation of VEGFAZebrafish developmentEmbryonic developmentTarget protectorNovel functionPrecise regulationGene expressionMorphogenetic activityDevelopmental angiogenesisPutative targetsRegulate angiogenesisEssential processMiR-206Physiological responsesCellular communicationVEGFA expressionGrowth factorVascular endothelial growth factorExpressionAngiogenesisMir-33 regulates cell proliferation and cell cycle progression
Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan A, Esplugues E, Fernández-Hernando C. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012, 11: 922-933. PMID: 22333591, PMCID: PMC3323796, DOI: 10.4161/cc.11.5.19421.Peer-Reviewed Original ResearchConceptsCell cycle progressionCyclin-dependent kinase 6Cycle progressionCell proliferationCell cycle regulationMiR-33Expression of genesCyclin D1Cell cycle arrestSREBP genesCycle regulationFatty acid metabolismHost genesPosttranscriptional levelGene expressionIntronic sequencesKinase 6Cellular growthCritical regulatorCycle arrestCellular levelLiver regenerationGenesMiR-33 expressionAcid metabolism
2011
The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism
Moore KJ, Rayner KJ, Suárez Y, Fernández-Hernando C. The Role of MicroRNAs in Cholesterol Efflux and Hepatic Lipid Metabolism. Annual Review Of Nutrition 2011, 31: 49-63. PMID: 21548778, PMCID: PMC3612434, DOI: 10.1146/annurev-nutr-081810-160756.Peer-Reviewed Original ResearchConceptsGene expressionSterol response element-binding proteinMiR-33Fatty acid β-oxidationElement-binding proteinFatty acid homeostasisResponse element-binding proteinRole of microRNAsCholesterol effluxIntronic miRNALipid metabolismRNA bindsPosttranscriptional controlUntranslated regionAbundant miRNABiological processesElegant mechanismMiR-122Lipid homeostasisΒ-oxidationAcid homeostasisCell phenotypeMiRNAsHepatic lipid metabolismMicroRNAs
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, CulturedE-SelectinEndothelial CellsFeedback, 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-1Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair
Yu J, Fernández-Hernando C, Suarez Y, Schleicher M, Hao Z, Wright PL, DiLorenzo A, Kyriakides TR, Sessa WC. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 17511-17516. PMID: 19805174, PMCID: PMC2762666, DOI: 10.1073/pnas.0907359106.Peer-Reviewed Original ResearchConceptsBlood vessel assemblyBone marrow-derived macrophagesBone marrow reconstitution experimentsMarrow-derived macrophagesRac activationBlood vessel formationGene expressionReconstitution experimentsMacrophage infiltrationInflammatory gene expressionVessel formationBlood flow recoveryMacrophage-mediated inflammationTissue repairMyeloid cellsBlood flow controlVessel assemblyLimb ischemiaFunctional recoveryInflammatory responseReticulon 4BWound healingIschemiaFlow recoveryGenesMicroRNAs As Novel Regulators of Angiogenesis
Suárez Y, Sessa WC. MicroRNAs As Novel Regulators of Angiogenesis. Circulation Research 2009, 104: 442-454. PMID: 19246688, PMCID: PMC2760389, DOI: 10.1161/circresaha.108.191270.Peer-Reviewed Original ResearchConceptsInvolvement of miRNAsShort noncoding RNAsPosttranscriptional regulationNoncoding RNAsNovel regulatorKey regulatorNegative regulatorGene expressionAspects of developmentNew blood vesselsRegulatorVascular biologyCurrent experimental evidencePotential therapeutic applicationsMiRNAsMicroRNAsAngiogenic processEndothelial cellsRegulationAbnormal angiogenesisTherapeutic applicationsAngiogenesisRNABiologyHomeostasis
2007
Dicer 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