2022
Antagonism of miR-148a attenuates atherosclerosis progression in APOB TG Apobec -/- Ldlr +/- mice: A brief report
Rotllan N, Zhang X, Canfrán-Duque A, Goedeke L, Griñán R, Ramírez CM, Suárez Y, Fernández-Hernando C. Antagonism of miR-148a attenuates atherosclerosis progression in APOB TG Apobec -/- Ldlr +/- mice: A brief report. Biomedicine & Pharmacotherapy 2022, 153: 113419. PMID: 36076541, PMCID: PMC11140622, DOI: 10.1016/j.biopha.2022.113419.Peer-Reviewed Original ResearchConceptsProgression of atherosclerosisMiR-148aLipoprotein cholesterolAtherosclerotic lesionsHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolAnti-inflammatory effectsAnti-inflammatory genesMacrophage cholesterol effluxWestern-style dietMiR-148a levelsHepatic gene expressionMurine primary macrophagesAntiatherogenic effectsAtherosclerosis progressionInflammatory responseTherapeutic silencingLipoprotein metabolismPlaque stabilityCholesterol effluxPrimary macrophagesPlaque sizeCholesterol homeostasisLesionsMRNA levels
2021
Loss 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
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 ResearchConceptsMacrophage 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 targetMacrophagesMacrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis
Canfrán‐Duque A, Rotllan N, Zhang X, Fernández‐Fuertes M, Ramírez‐Hidalgo C, Araldi E, Daimiel L, Busto R, Fernández‐Hernando C, Suárez Y. Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Molecular Medicine 2017, 9: 1244-1262. PMID: 28674080, PMCID: PMC5582411, DOI: 10.15252/emmm.201607492.Peer-Reviewed Original ResearchConceptsER stress-induced apoptosisPost-translational degradationFoam cell formationMiR-21MiR-21 target genesTarget genesJNK signalingPlaque necrosisAbundant miRNAVascular inflammationAccumulation of lipidsHematopoietic cellsMacrophage apoptosisCell formationAberrant expressionMacrophage deficiencyApoptosisCholesterol effluxProgression of atherosclerosisChronic inflammatory diseasePathophysiological processesInflammatory cellsExpressionInflammatory diseasesCardiovascular disease
2016
Micro-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.BooksConceptsReverse 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 efflux
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 levelsThe 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
2010
microRNAs and cholesterol metabolism
Moore KJ, Rayner KJ, Suárez Y, Fernández-Hernando C. microRNAs and cholesterol metabolism. Trends In Endocrinology And Metabolism 2010, 21: 699-706. PMID: 20880716, PMCID: PMC2991595, DOI: 10.1016/j.tem.2010.08.008.Peer-Reviewed Original ResearchConceptsPotent post-transcriptional regulatorsPost-transcriptional regulatorsMiR-33Non-coding RNALipid metabolism genesCholesterol metabolismTranscriptional regulationEpigenetic regulationFatty acid metabolismABC transportersMetabolism genesHDL biogenesisCellular levelCholesterol homeostasisMicroRNAsAcid metabolismImportant roleMiR-370Cholesterol effluxMetabolismMiR-122RegulationNew avenuesBiogenesisGenesMiR-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