2019
Specific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development
Price NL, Rotllan N, Zhang X, Canfrán-Duque A, Nottoli T, Suarez Y, Fernández-Hernando C. Specific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development. Circulation Research 2019, 124: 874-880. PMID: 30707082, PMCID: PMC6417928, DOI: 10.1161/circresaha.118.314415.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter 1Binding SitesCholesterolMacrophagesMiceMice, KnockoutMicroRNAsPlaque, AtheroscleroticReceptors, LDLConceptsMacrophage cholesterol effluxAtherosclerotic plaque formationCholesterol effluxMiR-33Proatherogenic effectsABCA1 expressionBone marrowDeficient animalsPlaque formationMiR-33-deficient miceHigh-fat diet feedingHepatic ABCA1 expressionAtherosclerotic plaque burdenFat diet feedingDevelopment of obesityNovel mouse modelAtherosclerotic plaque developmentFoam cell formationPlaque burdenDeficient miceDiet feedingMetabolic dysfunctionSpecific disruptionMouse modelKnockout mice
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
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 effluxMicroRNA-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 1
2013
Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Ramírez CM, Rotllan N, Vlassov AV, Dávalos A, Li M, Goedeke L, Aranda JF, Cirera-Salinas D, Araldi E, Salerno A, Wanschel A, Zavadil J, Castrillo A, Kim J, Suárez Y, Fernández-Hernando C. Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144. Circulation Research 2013, 112: 1592-1601. PMID: 23519695, PMCID: PMC3929583, DOI: 10.1161/circresaha.112.300626.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticholesteremic AgentsApolipoprotein A-IATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersChlorocebus aethiopsCholesterol, HDLCOS CellsDiet, High-FatGene Expression ProfilingHep G2 CellsHepatocytesHomeostasisHumansHydrocarbons, FluorinatedLiver X ReceptorsMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsOligonucleotide Array Sequence AnalysisOligonucleotidesOrphan Nuclear ReceptorsSulfonamidesConceptsAdenosine triphosphate-binding cassette transporter A1Liver X nuclear receptorCholesterol metabolismABCA1 expressionMiR-144HDL levelsLXR agonistsCholesterol effluxLXR ligandsHigh-density lipoprotein levelsPlasma high-density lipoprotein levelsTriphosphate-binding cassette transporter A1Potential therapeutical interventionsAtherosclerotic vascular diseaseMacrophage cholesterol effluxCassette transporter A1Cassette transporter G1MiR-144 expressionPrimary mouse peritoneal macrophagesHigh-density lipoprotein biogenesisEfflux of cholesterolFoam cell formationAdenosine triphosphate-binding cassette transportersModulation of miRNAsMiRNA expression signatures
2011
MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1
Ramirez CM, Dávalos A, Goedeke L, Salerno AG, Warrier N, Cirera-Salinas D, Suárez Y, Fernández-Hernando C. MicroRNA-758 Regulates Cholesterol Efflux Through Posttranscriptional Repression of ATP-Binding Cassette Transporter A1. Arteriosclerosis Thrombosis And Vascular Biology 2011, 31: 2707-2714. PMID: 21885853, PMCID: PMC3298756, DOI: 10.1161/atvbaha.111.232066.Peer-Reviewed Original ResearchConceptsATP-binding cassette transporter A1Cassette transporter A1Posttranscriptional regulationCellular cholesterol effluxUnbiased genome-wide screenMiR-758Cholesterol effluxGenome-wide screenExpression of ABCA1Cholesterol-loaded macrophagesIntracellular cholesterol accumulationPosttranscriptional repressionNovel miRNABioinformatics analysisMouse cellsMajor regulatorHuman cellsLuciferase reporterMacrophage cholesterol effluxMouse peritoneal macrophagesPeritoneal macrophagesABCA1 geneABCA1 expressionQuantitative real-time reverse transcription-polymerase chain reactionHigh-density lipoprotein levelsAntagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis
Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. Journal Of Clinical Investigation 2011, 121: 2921-2931. PMID: 21646721, PMCID: PMC3223840, DOI: 10.1172/jci57275.Peer-Reviewed Original ResearchConceptsABC transporter A1HDL levelsRegression of atherosclerosisCholesterol transportMiR-33MiR-33 inhibitionAtherosclerotic vascular diseasePlasma HDL levelsInflammatory gene expressionReverse cholesterol transportABCA1 levelsAtherosclerosis regressionVascular diseasePlaque macrophagesPlaque stabilityABCA1 expressionAtherosclerotic plaquesMice promotesProtective roleLipid metabolismLDL receptorClinical therapyPlaque sizeAtherosclerosisSREBF2 gene
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