2021
MicroRNA 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 ResearchMeSH KeywordsAtherosclerosisBiological TransportCardiovascular DiseasesCholesterolGene Expression RegulationHumansLipid MetabolismLipoproteins, HDLLipoproteins, LDLLipoproteins, VLDLMicroRNAsConceptsDifferent cell typesCell typesMultiple mRNA targetsCholesterol homeostasisSmall noncoding RNAsMicroRNA activityCholesterol-laden cellsMicroRNA regulationCholesterol metabolismMRNA targetsNoncoding RNAsPosttranscriptional levelGene expressionSpecialized functionsMicroRNAsCurrent knowledgeTarget interactionsHomeostasisMetabolismPathwayExpressionMultiple stagesRNARegulationDistinctive effectsLoss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Price NL, Zhang X, Fernández-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfrán-Duque A, Aryal B, Mayr M, Suárez Y, Fernández-Hernando C. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2006478118. PMID: 33495342, PMCID: PMC7865172, DOI: 10.1073/pnas.2006478118.Peer-Reviewed Original ResearchConceptsMiR-33 deficiencyHDL-C levelsMiR-33Body weightAtherosclerotic plaque sizeAtherosclerotic plaque burdenDevelopment of fibrosisCholesterol transport capacityCholesterol transporter ABCA1High-density lipoprotein biogenesisSREBP2 transcription factorKnockout mouse modelConditional knockout mouse modelPlaque burdenCardiometabolic diseasesChow dietLiver functionMetabolic dysfunctionHDL metabolismHyperlipidemic conditionsMouse modelGlucose homeostasisCholesterol effluxLipid metabolismObesity
2018
Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearanceNon-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 atherosclerosisBiologyGenetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance
Price NL, Singh AK, Rotllan N, Goedeke L, Wing A, Canfrán-Duque A, Diaz-Ruiz A, Araldi E, Baldán Á, Camporez JP, Suárez Y, Rodeheffer MS, Shulman GI, de Cabo R, Fernández-Hernando C. Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance. Cell Reports 2018, 22: 2133-2145. PMID: 29466739, PMCID: PMC5860817, DOI: 10.1016/j.celrep.2018.01.074.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAdiposityAnimalsCholesterol, HDLCholesterol, LDLEatingEnzyme ActivationGene DeletionGene Expression RegulationGenetic Predisposition to DiseaseGerm CellsInflammation MediatorsInsulin ResistanceLipid MetabolismLiverMice, Inbred C57BLMicroRNAsModels, BiologicalObesityProtein Kinase C-epsilonSterol Regulatory Element Binding Protein 1ConceptsMiR-33Insulin resistanceFood intakeIncreases food intakeAdipose tissue expansionKey metabolic tissuesWild-type animalsPromotes obesityImpaired lipolysisPair feedingCardiovascular diseaseMetabolic dysfunctionTherapeutic modulationAdipose tissueLipid uptakeMiRNA-based therapiesMetabolic tissuesGenetic ablationTissue expansionMiceObesityTherapyDeleterious effectsDiseasePrevious reports
2017
Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins
Singh AK, Aryal B, Zhang X, Fan Y, Price NL, Suárez Y, Fernández-Hernando C. Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins. Seminars In Cell And Developmental Biology 2017, 81: 129-140. PMID: 29183708, PMCID: PMC5975105, DOI: 10.1016/j.semcdb.2017.11.026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiovascular DiseasesGene Expression RegulationHomeostasisHumansLipid MetabolismMicroRNAsRNA, Long NoncodingRNA-Binding ProteinsConceptsLipid metabolismNon-coding RNAImportance of microRNAsNumber of miRNAsRole of lncRNAsLipid-related genesTranscriptional regulationCoding RNAsPosttranscriptional regulationPosttranscriptional levelMiRNA expressionHigh abundanceLncRNAsRNACholesterol homeostasisMiR-33MiR-148aSpecific roleMiRNAsRegulationLipoprotein metabolismRecent findingsMetabolismProteinExpression
2016
Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease
Montenont E, Echagarruga C, Allen N, Araldi E, Suarez Y, Berger JS. Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease. Blood 2016, 128: 2033-2042. PMID: 27609643, PMCID: PMC5073182, DOI: 10.1182/blood-2016-03-703157.Peer-Reviewed Original ResearchMeSH KeywordsAdultAtherosclerosisBlood PlateletsCell LineCytoskeletonFemaleGene Expression RegulationHumansMaleMegakaryocytesMicrofilament ProteinsPlatelet AdhesivenessConceptsPlatelet activityCardiovascular diseaseMEG-01 cellsHyperreactive platelet phenotypeBasal intracellular calcium concentrationPathogenesis of atherothrombosisSex-matched controlsIntracellular calcium concentrationMessenger RNAMEG-01Healthy controlsClinical significancePlatelet-related genesPlatelet phenotypeBasal stateMegakaryoblastic cell line MEG-01Human megakaryoblastic cell line MEG-01Thrombin activationDiseaseCalcium concentrationKD phenotypeProtein levelsF-actin contentPlatelet messenger RNAPlatelet RNAMicro-RNAs and High-Density Lipoprotein Metabolism
Canfrán-Duque A, Lin CS, Goedeke L, Suárez Y, Fernández-Hernando C. Micro-RNAs and High-Density Lipoprotein Metabolism. Arteriosclerosis Thrombosis And Vascular Biology 2016, 36: 1076-1084. PMID: 27079881, PMCID: PMC5315356, DOI: 10.1161/atvbaha.116.307028.BooksMeSH KeywordsAnimalsBiological TransportCardiovascular DiseasesDyslipidemiasGene Expression RegulationGenetic MarkersHumansLipoproteins, HDLMicroRNAsPredictive Value of TestsPrognosisConceptsReverse cholesterol transportCardiovascular diseaseHDL metabolismCholesterol transportIschemic heart diseaseCause of deathEarlier epidemiological studiesPotential therapeutic targetBile acid synthesisMicro-RNAsCardioprotective effectsHeart diseaseEpidemiological studiesImproved preventionCholesterol effluxTherapeutic targetDensity lipoproteinCholesterol uptakeDiseaseArtery wallHDL biogenesisInverse correlationHDLLiverAcid synthesis
2015
miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice
Goedeke L, Rotllan N, Ramírez CM, Aranda JF, Canfrán-Duque A, Araldi E, Fernández-Hernando A, Langhi C, de Cabo R, Baldán Á, Suárez Y, Fernández-Hernando C. miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice. Atherosclerosis 2015, 243: 499-509. PMID: 26520906, PMCID: PMC4975922, DOI: 10.1016/j.atherosclerosis.2015.09.033.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdaptor Proteins, Signal TransducingAnimalsATP Binding Cassette Transporter 1BiomarkersChlorocebus aethiopsCholesterolComputational BiologyCOS CellsDatabases, GeneticDiet, High-FatGene Expression RegulationGene Regulatory NetworksHep G2 CellsHumansLiverMacaca mulattaMaleMice, Inbred C57BLMicroRNAsReceptors, LDLTime FactorsTransfectionTriglyceridesConceptsWild-type miceHepatic lipid levelsMiR-27b expressionLipid levelsHepatic lipidsABCA1 expressionMiR-27bWeeks of treatmentExpression of ABCA1Potential therapeutic targetABCA1 protein levelsCellular cholesterol effluxMiR-27b functionsMiR-27b overexpressionMouse hepatic cellsHepatic LDLRHepatic ABCA1Human hepatic Huh7 cellsHepatic cholesterolWestern dietCardiovascular diseaseTherapeutic administrationLDLR expressionTreatment groupsCholesterol effluxVEGF-Induced Expression of miR-17–92 Cluster in Endothelial Cells Is Mediated by ERK/ELK1 Activation and Regulates Angiogenesis
Chamorro-Jorganes A, Lee MY, Araldi E, Landskroner-Eiger S, Fernández-Fuertes M, Sahraei M, del Rey M, van Solingen C, Yu J, Fernández-Hernando C, Sessa WC, Suárez Y. VEGF-Induced Expression of miR-17–92 Cluster in Endothelial Cells Is Mediated by ERK/ELK1 Activation and Regulates Angiogenesis. Circulation Research 2015, 118: 38-47. PMID: 26472816, PMCID: PMC4703066, DOI: 10.1161/circresaha.115.307408.Peer-Reviewed Original ResearchConceptsMiR-17Elk1 activationEndothelial angiogenic functionEC proliferationRegulation of angiogenesisTranscription activationTranscriptional programsGenetic evidenceCluster expressionTumor angiogenesisAngiogenic sproutingVEGF stimulationRescue experimentsRetinal angiogenesisRegulate angiogenesisLines of evidenceEndothelial cell functionAngiogenic switchPhysiological retinal angiogenesisAngiogenic functionDevelopmental retinal angiogenesisCell functionTumor developmentRegulationCrucial mediatorMicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels
Goedeke L, Rotllan N, Canfrán-Duque A, Aranda JF, Ramírez CM, Araldi E, Lin CS, Anderson NN, Wagschal A, de Cabo R, Horton JD, Lasunción MA, Näär AM, Suárez Y, Fernández-Hernando C. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nature Medicine 2015, 21: 1280-1289. PMID: 26437365, PMCID: PMC4711995, DOI: 10.1038/nm.3949.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter 1Cholesterol, HDLCholesterol, LDLGene Expression RegulationHep G2 CellsHepatocytesHigh-Throughput Screening AssaysHumansLiverMiceMicroRNAsReceptors, LDLRNA Processing, Post-TranscriptionalSignal TransductionSterol Regulatory Element Binding Protein 1Disruption of the mevalonate pathway induces dNTP depletion and DNA damage
Sánchez C, Martín J, Jin JS, Dávalos A, Zhang W, de la Peña G, Martínez-Botas J, Rodríguez-Acebes S, Suárez Y, Hazen MJ, Gómez-Coronado D, Busto R, Cheng YC, Lasunción MA. Disruption of the mevalonate pathway induces dNTP depletion and DNA damage. Biochimica Et Biophysica Acta 2015, 1851: 1240-1253. PMID: 26055626, DOI: 10.1016/j.bbalip.2015.06.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCarboxy-LyasesCell Cycle CheckpointsCell Line, TumorCell ProliferationCheckpoint Kinase 1DeoxyribonucleosidesDNA DamageDNA ReplicationGene Expression RegulationHalogenationHemiterpenesHistonesHL-60 CellsHumansLymphocytesMevalonic AcidOrganophosphorus CompoundsProtein KinasesRNA, Small InterferingSignal TransductionConceptsMevalonate diphosphate decarboxylaseDiphosphate decarboxylaseCell cycle progressionDNA replicationCycle progressionMevalonate pathwayDNA damageDNA damage responseNon-sterol isoprenoidsCell proliferationInhibition of Chk1Cholesterol biosynthesis pathwayMassive cell deathSubsequent DNA damageΓ-H2AX formationCell cycle arrestReplication stressBiosynthesis pathwayΓ-H2AX fociChk1 activationDamage responseIsopentenyl diphosphateMitosis completionCell divisionDNTP depletionThe 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 ResearchMeSH KeywordsAnimalsCaveolin 1Chlorocebus aethiopsClathrin Heavy ChainsCOS CellsDynaminsEndocytosisGene Expression RegulationHeLa CellsHumansMicroRNAsRab5 GTP-Binding ProteinsConceptsClathrin 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 ResearchMeSH KeywordsAnimalsCardiovascular DiseasesCell DifferentiationEndothelial CellsEndothelium, VascularGene Expression RegulationGene TargetingGenetic TherapyHemodynamicsHumansMicroRNAsConceptsEndothelial 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 traffickingRegulatorTargetMicroRNAs in Metabolic Disease
Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y. MicroRNAs in Metabolic Disease. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 178-185. PMID: 23325474, PMCID: PMC3740757, DOI: 10.1161/atvbaha.112.300144.BooksMeSH KeywordsAnimalsCarbohydrate MetabolismGene Expression RegulationGenetic TherapyGlucoseHomeostasisHumansInsulinLipid MetabolismMetabolic DiseasesMicroRNAsSignal TransductionConceptsContribution of miRNAsCellular cholesterol exportMiR-33Fatty acid degradationSREBP genesIntronic miRNAMetabolic diseasesFatty acid synthesisHost genesCholesterol exportSpecific miRNAsPhysiological processesLipid homeostasisMiRNAsAcid synthesisAcid degradationCardiometabolic diseasesGenesMicroRNAsGlucose homeostasisCritical roleGlucose metabolismLipoprotein secretionRecent findingsMetabolic control
2010
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner KJ, Suárez Y, Dávalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernández-Hernando C. MiR-33 Contributes to the Regulation of Cholesterol Homeostasis. Science 2010, 328: 1570-1573. PMID: 20466885, PMCID: PMC3114628, DOI: 10.1126/science.1189862.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein A-IATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1ATP-Binding Cassette TransportersCarrier ProteinsCell LineCholesterolCholesterol, DietaryDietary FatsGene Expression RegulationHomeostasisHumansHypercholesterolemiaIntracellular Signaling Peptides and ProteinsIntronsLipoproteinsLipoproteins, HDLLiverMacrophagesMacrophages, PeritonealMembrane GlycoproteinsMiceMice, Inbred C57BLMicroRNAsNiemann-Pick C1 ProteinProteinsSterol Regulatory Element Binding Protein 2TransfectionConceptsSterol regulatory element-binding factor-2MiR-33Cellular cholesterol transportCholesterol effluxExpression of genesIntronic microRNAsTranscriptional regulatorsTriphosphate-binding cassette transportersAdenosine triphosphate-binding cassette transportersCellular cholesterol effluxCassette transportersHDL biogenesisHuman cellsCellular levelCholesterol homeostasisABCA1 expressionFactor 2Mouse macrophagesGenesLentiviral deliveryCholesterol transportExpressionABCA1Cholesterol metabolismEfflux
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-1MicroRNAs 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