2024
Deletion of miR‐33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice
Tate M, Wijeratne H, Kim B, Philtjens S, You Y, Lee D, Gutierrez D, Sharify D, Wells M, Perez‐Cardelo M, Doud E, Fernandez‐Hernando C, Lasagna‐Reeves C, Mosley A, Kim J. Deletion of miR‐33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice. Alzheimer's & Dementia 2024, 20: 7805-7818. PMID: 39345217, DOI: 10.1002/alz.14243.Peer-Reviewed Original ResearchAmyloid-betaAlzheimer's diseaseMicroglial migrationAmyloid mouse modelMiR-33Multi-omics studiesABCA1 levelsPotential drug targetsIncreased ABCA1 protein levelsMicroRNA-33ApoE lipidationProteomic changesRNA sequencingMulti-omicsNeuropathological phenotypeAmyloid pathologyInhibition of miR-33APP/PS1 micePhagocytosis in vitroRare variantsApolipoprotein EDrug targetsABCA1 protein levelsAmyloidPlaque depositionmiR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression
Fernández-Tussy P, Cardelo M, Zhang H, Sun J, Price N, Boutagy N, Goedeke L, Cadena-Sandoval M, Xirouchaki C, Brown W, Yang X, Pastor-Rojo O, Haeusler R, Bennett A, Tiganis T, Suárez Y, Fernández-Hernando C. miR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression. JCI Insight 2024, 9: e168476. PMID: 39190492, PMCID: PMC11466198, DOI: 10.1172/jci.insight.168476.Peer-Reviewed Original ResearchMiR-33Regulation of biological processesMitochondrial fatty acid oxidationRegulation of lipid metabolismNon-alcoholic fatty liver diseaseDevelopment of effective therapeuticsFatty acid oxidationLipid synthesisProgression of non-alcoholic fatty liver diseaseMitochondrial functionTarget genesBiological processesComplex diseasesNon-alcoholic steatohepatitisLipid accumulationDeletionDevelopment of non-alcoholic fatty liver diseasePathway activationLipid metabolismProgress to non-alcoholic steatohepatitisAcid oxidationHCC progressionEffective therapeuticsTherapeutic targetHepatocellular carcinomamicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Price N, Fernández-Tussy P, Varela L, Cardelo M, Shanabrough M, Aryal B, de Cabo R, Suárez Y, Horvath T, Fernández-Hernando C. microRNA-33 controls hunger signaling in hypothalamic AgRP neurons. Nature Communications 2024, 15: 2131. PMID: 38459068, PMCID: PMC10923783, DOI: 10.1038/s41467-024-46427-0.Peer-Reviewed Original ResearchConceptsAgRP neuronsFeeding behaviorFatty acid metabolismNon-coding RNAsMitochondrial biogenesisRegulatory pathwaysTarget genesHypothalamic AgRP neuronsExcessive nutrient intakeCentral regulatorBioenergetic processesAcid metabolismActivation of AgRP neuronsModulate feeding behaviorCentral regulation of feeding behaviorRegulation of feeding behaviorMiR-33Hunger signalsMicroRNA-33Metabolic diseasesAlternative therapeutic approachLoss of miR-33Mouse modelMetabolic dysfunctionRegulation
2023
microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouse
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
2020
Uncovering the Specific Functions of miR-33 in Regulation of Feeding and Cardiometabolic Diseases Linked to Aging
Price N, Zhang X, Fernandez-Tussy P, de Cabo R, Fernandez-Hernando C. Uncovering the Specific Functions of miR-33 in Regulation of Feeding and Cardiometabolic Diseases Linked to Aging. Innovation In Aging 2020, 4: 128-128. PMCID: PMC7741365, DOI: 10.1093/geroni/igaa057.421.Peer-Reviewed Original ResearchMiR-33Cardiometabolic diseasesMetabolic dysfunctionHigh fat diet fed miceFat Diet-Fed MiceMetabolic tissuesDiet fed miceDevelopment of obesityMacrophage cholesterol effluxDevelopment of atherosclerosisRegulation of feedingCholesterol transporter ABCA1Unique mouse modelKey metabolic tissuesDifferent metabolic tissuesFeeding behaviorFed miceHeart diseaseInflammatory responseMouse modelRelated health issuesCholesterol effluxKnockout miceDeficient animalsAtherosclerosis
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
2018
Genetic 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
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
2010
microRNAs, Plasma Lipids, and Cardiovascular Disease
Dávalos A, Fernández-Hernando C. microRNAs, Plasma Lipids, and Cardiovascular Disease. Current Cardiovascular Risk Reports 2010, 5: 10-17. DOI: 10.1007/s12170-010-0145-1.Peer-Reviewed Original ResearchCardiovascular diseaseShort non-coding RNAsPost-transcriptional repressionHigh-density lipoprotein biogenesisMiR-33Non-coding RNAsTotal cholesterol levelsCassette transporter A1Expression of ATPMiR-122 expressionAberrant regulationGene expressionLipoprotein biogenesisDyslipidemic patientsLipid homeostasisMetabolic syndromePlasma lipidsCholesterol levelsLeading causeLipoprotein metabolismABCG1 transportersCholesterol effluxCholesterol metabolismPathologic processesMultifactorial disorderMiR-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