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 SREBP2
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 targetMacrophages
2016
Age‐associated vascular inflammation promotes monocytosis during atherogenesis
Du W, Wong C, Song Y, Shen H, Mori D, Rotllan N, Price N, Dobrian AD, Meng H, Kleinstein SH, Fernandez‐Hernando C, Goldstein DR. Age‐associated vascular inflammation promotes monocytosis during atherogenesis. Aging Cell 2016, 15: 766-777. PMID: 27135421, PMCID: PMC4933655, DOI: 10.1111/acel.12488.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAortaAtherosclerosisBlood VesselsCell CountChemotaxisCulture Media, ConditionedDiet, High-FatDown-RegulationHematopoiesisHemodynamicsInflammationInflammation MediatorsInsulin ResistanceInterleukin-6LeukocytosisMacrophagesMaleMiceMice, Inbred C57BLMonocytesOligonucleotide Array Sequence AnalysisReceptors, LDLStromal CellsUp-RegulationConceptsHigh-fat dietVascular inflammationMacrophage accumulationAtherosclerotic aortaBone marrow transplant experimentsStromal factorsElevated blood pressureVascular smooth muscle cellsLow-fat dietSmooth muscle cellsBlood pressurePeripheral monocytosisProinflammatory stateInflammatory stateLDL levelsIL-6Insulin resistancePeripheral bloodEnhanced atherogenesisInflammatory responseMetabolic dysfunctionYoung aortasMurine modelProduction of osteopontinCCL-2
2015
MicroRNA-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
2014
Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis
Rodlan N, Chamorro‐Jorganes A, Araldi E, Wanschel AC, Aryal B, Aranda JF, Goedeke L, Salerno AG, Ramírez CM, Sessa WC, Suárez Y, Fernández‐Hernando C. Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis. The FASEB Journal 2014, 29: 597-610. PMID: 25392271, PMCID: PMC4314230, DOI: 10.1096/fj.14-262097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlood GlucoseBone Marrow CellsBone Marrow TransplantationCell MovementCholesterolCytokinesDisease ProgressionInflammationInsulinLeukocytesLipidsLipoproteins, LDLMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalMicroscopy, FluorescencePlaque, AtheroscleroticProto-Oncogene Proteins c-aktReceptors, LDLConceptsProgression of atherosclerosisSerine-threonine protein kinaseBone marrow cellsAkt2-deficient miceInsulin-responsive tissuesWild-type bone marrow cellsProtein kinaseMarrow cellsAkt2 deficiencyAkt2Higher plasma lipidsWild-type miceMice resultsProatherogenic cytokinesObese subjectsPlasma lipidsProinflammatory cytokinesInsulin resistanceInflammatory responseGlucose levelsAtherosclerotic plaquesCholesterol metabolismAtherosclerosisMacrophage migrationMarked reduction