2024
Abstract 129: Hypercholesterolemia-induced Lxr Signaling In Smc Contributes To Atherosclerotic Lesion Remodeling And Regulates Vascular And Visceral Smc Function
Zhang H, Biwer L, de Urturi D, Fernandez-Tussy P, Jovin D, Huang Y, Zhang X, Esplugues E, Greif D, Suarez Y, Fernandez-Hernando C. Abstract 129: Hypercholesterolemia-induced Lxr Signaling In Smc Contributes To Atherosclerotic Lesion Remodeling And Regulates Vascular And Visceral Smc Function. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a129-a129. DOI: 10.1161/atvb.44.suppl_1.129.Peer-Reviewed Original ResearchLiver X receptorTranscription factorsVascular smooth muscle cellsRegulation of lipid metabolismLXR signalingB geneScRNA-seqFate decisionsSignaling eventsSMC functionGene expressionActivation of liver X receptorCell statesLesion remodelingCharacterized miceLipid metabolismLineage tracingPhenotypic switchingX receptorReduced fibrous cap thicknessTranscriptionFeatures of plaque instabilitySmooth muscle cellsLipid absorptionProgression of atherosclerosis
2022
Antagonism 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 ResearchConceptsProgression 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 levels
2021
Deficiency 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
2018
Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis
Aryal B, Singh AK, Zhang X, Varela L, Rotllan N, Goedeke L, Chaube B, Camporez JP, Vatner DF, Horvath TL, Shulman GI, Suárez Y, Fernández-Hernando C. Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI Insight 2018, 3: e97918. PMID: 29563332, PMCID: PMC5926923, DOI: 10.1172/jci.insight.97918.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose TissueAllelesAngiopoietin-Like Protein 4AnimalsAtherosclerosisBody WeightChemokinesCytokinesDiet, High-FatDiet, WesternFatty AcidsGene Expression ProfilingGene Expression RegulationGene Knockout TechniquesGlucoseInsulinIntegrasesIntercellular Signaling Peptides and ProteinsLipid MetabolismLipoprotein LipaseLipoproteinsLiverMaleMiceMice, Inbred C57BLMice, KnockoutMusclesObesityProprotein Convertase 9TriglyceridesConceptsAngiopoietin-like protein 4High-fat dietEctopic lipid depositionLipid depositionGlucose toleranceLipoprotein lipaseShort-term high-fat dietSevere metabolic abnormalitiesProgression of atherosclerosisMajor risk factorTriacylglycerol-rich lipoproteinsFatty acid uptakeAdipose tissue resultsProatherogenic lipoproteinsCardiometabolic diseasesMetabolic abnormalitiesKO miceRisk factorsWhole body lipidMetabolic disordersGlucose metabolismLPL activityAdipose tissueGenetic ablationRapid clearance
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 targetMacrophagesMacrophage 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
2015
Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease.
Araldi E, Chamorro-Jorganes A, van Solingen C, Fernandez-Hernando C, Suarez Y. Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease. Current Vascular Pharmacology 2015, 13: 291-304. PMID: 26156264, DOI: 10.2174/15701611113119990012.Peer-Reviewed Original ResearchConceptsPost-transcriptional levelMonocyte-derived phagocytesFoam cell formationGene regulatorsCell adhesion moleculeModulating microRNAsVascular smooth muscle cellsCell differentiationArterial tree resultsVascular diseaseCell formationMicroRNAsSmooth muscle cellsCap formationVascular cellsFibrous cap formationPotential therapeutic applicationsUnstable fibrous capUnstable coronary syndromesAtherosclerotic vascular diseaseTree resultsMuscle cellsChronic inflammatory diseaseProgression of atherosclerosisLesion-prone sites
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
2013
Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease.
Araldi E, Chamorro-Jorganes A, van Solingen C, Fernández-Hernando C, Suárez Y. Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease. Current Vascular Pharmacology 2013 PMID: 23713860, PMCID: PMC3883893.Peer-Reviewed Original ResearchPost-transcriptional levelMonocyte-derived phagocytesFoam cell formationGene regulatorsCell adhesion moleculeModulating microRNAsVascular smooth muscle cellsCell differentiationArterial tree resultsVascular diseaseCell formationMicroRNAsSmooth muscle cellsCap formationVascular cellsFibrous cap formationPotential therapeutic applicationsUnstable fibrous capUnstable coronary syndromesAtherosclerotic vascular diseaseTree resultsMuscle cellsChronic inflammatory diseaseProgression of atherosclerosisLesion-prone sites
2009
Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis
Fernández-Hernando C, Yu J, Suárez Y, Rahner C, Dávalos A, Lasunción MA, Sessa WC. Genetic Evidence Supporting a Critical Role of Endothelial Caveolin-1 during the Progression of Atherosclerosis. Cell Metabolism 2009, 10: 48-54. PMID: 19583953, PMCID: PMC2735117, DOI: 10.1016/j.cmet.2009.06.003.Peer-Reviewed Original ResearchConceptsProgression of atherosclerosisInitiation of atherosclerosisCav-1ApoE knockout backgroundArtery wallKnockout backgroundLeukocyte adhesion moleculesNitric oxide productionEndothelial Cav-1 expressionCav-1 expressionEndothelial caveolin-1AtherosclerosisTransgenic miceOxide productionGenetic ablationLDL infiltrationAdhesion moleculesCritical roleCaveolin-1 geneLDL-derived cholesterolMiceVessel wallPhysiological evidenceLesion expansionGenetic evidence