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 formation
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
Macrophage 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
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