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 ResearchConceptsHematopoietic 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 lesionsGenes
2016
Chronic miR‐29 antagonism promotes favorable plaque remodeling in atherosclerotic mice
Ulrich V, Rotllan N, Araldi E, Luciano A, Skroblin P, Abonnenc M, Perrotta P, Yin X, Bauer A, Leslie KL, Zhang P, Aryal B, Montgomery RL, Thum T, Martin K, Suarez Y, Mayr M, Fernandez-Hernando C, Sessa WC. Chronic miR‐29 antagonism promotes favorable plaque remodeling in atherosclerotic mice. EMBO Molecular Medicine 2016, 8: 643-653. PMID: 27137489, PMCID: PMC4888854, DOI: 10.15252/emmm.201506031.Peer-Reviewed Original ResearchConceptsPlaque morphologyReduced lesion sizeAcute myocardial infarctionAtherosclerotic mouse modelVulnerable atherosclerotic lesionsFibrous cap thicknessPlaque extracellular matrixChronic administrationExtracellular matrixAtherosclerotic miceMyocardial infarctionPlaque remodelingSolid organsAbnormal remodelingMouse modelAtherosclerotic lesionsAtherosclerotic plaquesBlood chemistryLesion sizeMiR-29Necrotic zoneLesionsPlaquesCap thicknessMiR-29 target genes
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
2011
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis
Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, van Gils JM, Rayner AJ, Chang AN, Suarez Y, Fernandez-Hernando C, Fisher EA, Moore KJ. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. Journal Of Clinical Investigation 2011, 121: 2921-2931. PMID: 21646721, PMCID: PMC3223840, DOI: 10.1172/jci57275.Peer-Reviewed Original ResearchConceptsABC transporter A1HDL levelsRegression of atherosclerosisCholesterol transportMiR-33MiR-33 inhibitionAtherosclerotic vascular diseasePlasma HDL levelsInflammatory gene expressionReverse cholesterol transportABCA1 levelsAtherosclerosis regressionVascular diseasePlaque macrophagesPlaque stabilityABCA1 expressionAtherosclerotic plaquesMice promotesProtective roleLipid metabolismLDL receptorClinical therapyPlaque sizeAtherosclerosisSREBF2 gene