2022
Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling
Canfrán-Duque A, Rotllan N, Zhang X, Andrés-Blasco I, Thompson B, Sun J, Price N, Fernández-Fuertes M, Fowler J, Gómez-Coronado D, Sessa W, Giannarelli C, Schneider R, Tellides G, McDonald J, Fernández-Hernando C, Suárez Y. Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling. Circulation 2022, 147: 388-408. PMID: 36416142, PMCID: PMC9892282, DOI: 10.1161/circulationaha.122.059062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCholesterolHumansHydroxycholesterolsInflammationMacrophagesMiceMice, KnockoutPlaque, AtheroscleroticConceptsLipid-loaded macrophagesLineage-tracing mouse modelsSREBP transcriptional activityCholesterol biosynthetic intermediatesWestern diet feedingAccessible cholesterolDifferent macrophage populationsTranscriptomic analysisKey immune regulatorsPlasma membraneAtherosclerosis progressionImmune activationTranscriptional activityGene expressionDiet feedingInflammatory responseMouse bone marrowLiver X receptorBiosynthetic intermediatesSterol metabolismApoptosis susceptibilityToll-like receptor 4Proinflammatory gene expressionHuman coronary atherosclerotic lesionsMouse atherosclerotic plaquesAntagonism 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 ResearchMeSH KeywordsAnimalsAPOBEC DeaminasesApolipoproteins BAtherosclerosisCholesterol, HDLMiceMice, KnockoutMicroRNAsPlaque, AtheroscleroticReceptors, LDLConceptsProgression 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 levelsTargeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression
Zhang X, Rotllan N, Canfrán-Duque A, Sun J, Toczek J, Moshnikova A, Malik S, Price NL, Araldi E, Zhong W, Sadeghi MM, Andreev OA, Bahal R, Reshetnyak YK, Suárez Y, Fernández-Hernando C. Targeted Suppression of miRNA-33 Using pHLIP Improves Atherosclerosis Regression. Circulation Research 2022, 131: 77-90. PMID: 35534923, PMCID: PMC9640270, DOI: 10.1161/circresaha.121.320296.Peer-Reviewed Original ResearchConceptsMiR-33Gene expressionNature of miRNAsSingle-cell RNA sequencing analysisSingle-cell RNA transcriptomicsAnti-miRNA technologiesRNA sequencing analysisExpression of miRNAsRNA transcriptomicsNew therapeutic opportunitiesEntire pathwayMiRNA therapeuticsAtherosclerotic plaque macrophagesHuman diseasesMiRNAsSequencing analysisSpecific tissuesMetabolic tissuesTargeted suppressionMiR-33 inhibitionProtective miRNAsNumerous diseasesPharmacological inhibitionLipid accumulationTarget effects
2021
Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis
Zhang X, McDonald JG, Aryal B, Canfrán-Duque A, Goldberg EL, Araldi E, Ding W, Fan Y, Thompson BM, Singh AK, Li Q, Tellides G, Ordovás-Montanes J, García Milian R, Dixit VD, Ikonen E, Suárez Y, Fernández-Hernando C. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2107682118. PMID: 34782454, PMCID: PMC8617522, DOI: 10.1073/pnas.2107682118.Peer-Reviewed Original ResearchConceptsCholesterol biosynthetic intermediatesBiosynthetic intermediatesDependent inflammasome activationSingle-cell transcriptomicsMitochondrial reactive oxygen species productionFoam cell formationMacrophage foam cellsReactive oxygen species productionHuman coronary artery lesionsConversion of desmosterolTranscriptomic analysisMacrophage cholesterol metabolismPhysiological contextOxygen species productionLiver X receptor ligandsApoptosis-associated speck-like proteinRetinoid X receptor activationX receptor ligandsInflammasome activationAtherosclerotic plaquesSpeck-like proteinCholesterol homeostasisMacrophage inflammasome activationKey moleculesCell formationDeficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis
Zhang X, Sun J, Canfrán-Duque A, Aryal B, Tellides G, Chang YJ, Suárez Y, Osborne TF, Fernández-Hernando C. Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis. JCI Insight 2021, 6: e147984. PMID: 34003795, PMCID: PMC8262461, DOI: 10.1172/jci.insight.147984.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCells, CulturedCytokinesHistone-Lysine N-MethyltransferaseHumansInflammationMacrophagesMaleMicePlaque, AtheroscleroticTranscriptomeUp-RegulationConceptsHematopoietic cellsHistone methylation/acetylationSingle-cell RNA-seq analysisMethylation/acetylationHistone H3 Lys9RNA-seq analysisProgression of atherosclerosisEpigenetic marksLysine methyltransferasesH3 Lys9Epigenetic modificationsDNA methylationNoncoding RNAsCell regulatorsSETDB2Vascular inflammationAtherosclerotic lesionsAtherosclerotic plaquesMyeloid cell recruitmentGenetic deletionLDLR knockout miceEnhanced expressionHepatic lipid metabolismMurine atherosclerotic lesionsGenesLoss 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 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
2018
Non-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 atherosclerosisBiology
2016
ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression
Aryal B, Rotllan N, Araldi E, Ramírez CM, He S, Chousterman BG, Fenn AM, Wanschel A, Madrigal-Matute J, Warrier N, Martín-Ventura JL, Swirski FK, Suárez Y, Fernández-Hernando C. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature Communications 2016, 7: 12313. PMID: 27460411, PMCID: PMC4974469, DOI: 10.1038/ncomms12313.Peer-Reviewed Original ResearchMeSH KeywordsAngiopoietin-Like Protein 4AnimalsApoptosisAtherosclerosisBone Marrow TransplantationCell ProliferationCell SurvivalDisease ProgressionFoam CellsHematopoietic Stem CellsHumansInflammationLeukocytosisMacrophagesMaleMiceMice, Inbred C57BLModels, BiologicalMonocytesMyeloid Progenitor CellsPlaque, AtheroscleroticConceptsFoam cell formationMyeloid progenitor cell expansionANGPTL4 deficiencyCell formationMacrophage gene expressionLipid raft contentMyeloid progenitor populationsProgenitor cell expansionUpregulated genesProgenitor populationsGene expressionHaematopoietic cellsCell surfaceMacrophage apoptosisCell expansionCells resultsProtein 4Lipid accumulationCD36 expressionLike protein 4ExpressionProfound effectMacrophagesGenesLarger atherosclerotic plaques
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