2024
Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis
Joshi D, Coon B, Chakraborty R, Deng H, Yang Z, Babar M, Fernandez-Tussy P, Meredith E, Attanasio J, Joshi N, Traylor J, Orr A, Fernandez-Hernando C, Libreros S, Schwartz M. Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis. Nature Cardiovascular Research 2024, 3: 1035-1048. PMID: 39232138, PMCID: PMC11399086, DOI: 10.1038/s44161-024-00522-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCadherin Related ProteinsCadherinsDisease Models, AnimalEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, Inbred C57BLMice, KnockoutPlaque, AtheroscleroticReceptors, NotchSignal TransductionConceptsAtherosclerotic cardiovascular diseaseIntracellular domainNotch intracellular domainTranscription factor KLF2Mechanisms of vascular inflammationAnti-inflammatory programVascular endothelial cellsHost defenseCleavage resultsAntibody blockadeGenetic deletionVascular inflammationViral infectionImmune systemEndothelial cellsCardiovascular diseasePromote atherosclerosisBlood flowKLF2KLF4Suppressive signalsEndotheliumMechanistic studiesHeterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Ruz-Maldonado I, Gonzalez J, Zhang H, Sun J, Bort A, Kabir I, Kibbey R, Suárez Y, Greif D, Fernández-Hernando C. Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage. Nature Communications 2024, 15: 1247. PMID: 38341404, PMCID: PMC10858916, DOI: 10.1038/s41467-024-45439-0.Peer-Reviewed Original Research
2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2015
Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report
Goodwin JE, Zhang X, Rotllan N, Feng Y, Zhou H, Fernández-Hernando C, Yu J, Sessa WC. Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2015, 35: 779-782. PMID: 25810297, PMCID: PMC4375730, DOI: 10.1161/atvbaha.114.304525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisBody WeightBrachiocephalic TrunkCholesterolDiet, High-FatDisease Models, AnimalEndothelial CellsGenotypeMacrophagesMice, Inbred C57BLMice, KnockoutPhenotypeReceptors, GlucocorticoidSeverity of Illness IndexTime FactorsTriglyceridesConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorHigh-fat diet feedingApoE knockout backgroundSevere atherosclerotic lesionsGroups of micePathogenesis of atherosclerosisAortic sinusTotal cholesterolAtherosclerosis progressionBrachiocephalic arteryControl miceInflammatory milieuTonic inhibitionDiet feedingMacrophage recruitmentAtherosclerotic lesionsBody weightMiceKnockout backgroundReceptorsLesionsAtherosclerosisInflammationArtery
2012
Cardiovascular dysregulation of miR‐17‐92 causes a lethal hypertrophic cardiomyopathy and arrhythmogenesis
Danielson LS, Park DS, Rotllan N, Chamorro‐Jorganes A, Guijarro MV, Fernandez‐Hernando C, Fishman GI, Phoon CK, Hernando E. Cardiovascular dysregulation of miR‐17‐92 causes a lethal hypertrophic cardiomyopathy and arrhythmogenesis. The FASEB Journal 2012, 27: 1460-1467. PMID: 23271053, PMCID: PMC3606524, DOI: 10.1096/fj.12-221994.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrhythmias, CardiacCardiomyopathy, HypertrophicConnexin 43Disease Models, AnimalHeart Defects, CongenitalMiceMice, KnockoutMicroRNAsPTEN PhosphohydrolaseConceptsSmooth muscle tissueHypertrophic cardiomyopathyMiR-17Dose-dependent inductionMuscle tissueCardiovascular dysregulationArrhythmia inducibilityNovel direct targetMicroRNA cluster miR-17Lethal cardiomyopathyPremature mortalityTransgenic heartsMouse modelHeart sizeCluster miR-17CardiomyopathyPrecise mechanismLuciferase assayDirect targetExpression levelsPathological functionsExpression analysisConditional overexpressionTransgenic animalsHeartMicroRNAs regulating lipid metabolism in atherogenesis
Rayner K, Fernandez-Hernando C, Moore K. MicroRNAs regulating lipid metabolism in atherogenesis. Thrombosis And Haemostasis 2012, 107: 642-647. PMID: 22274626, PMCID: PMC3618663, DOI: 10.1160/th11-10-0694.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersCholesterolDisease Models, AnimalFatty AcidsGene Expression RegulationHumansLipid MetabolismLipoproteins, HDLLipoproteins, VLDLLiverMiceMicroRNAsModels, BiologicalSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2TriglyceridesConceptsSmall non-coding RNAsImportant post-transcriptional regulatorsCellular sterol levelsPost-transcriptional regulatorsNon-coding RNAsVariety of genesSterol response elementFatty acid homeostasisIntronic microRNAsLipid metabolismFatty acid synthesisHost genesTranscription factorsProtein geneCholesterol exportMetabolic programsKey regulatorFatty acid oxidationResponse elementHigh-density lipoproteinMicroRNAsRelated metabolic diseasesGenesABCA1 pathwayAcid homeostasis
2007
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WC. Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease. Cell Metabolism 2007, 6: 446-457. PMID: 18054314, PMCID: PMC3621848, DOI: 10.1016/j.cmet.2007.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAnimalsApolipoproteins EApoptosisAtherosclerosisBone Marrow TransplantationCoronary OcclusionDisease Models, AnimalEndothelial CellsFemaleHumansInflammation MediatorsMacrophagesMaleMiceMice, KnockoutNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktConceptsLoss of Akt1Apolipoprotein E knockout backgroundOcclusive coronary artery diseaseBone marrow transfer experimentsAcute coronary syndromeCoronary artery diseaseLesion expansionCoronary syndromeCoronary atherosclerosisSevere atherosclerosisArtery diseaseInflammatory mediatorsCoronary lesionsVascular protectionVascular originProinflammatory genesENOS phosphorylationCardiovascular systemLesion formationGenetic ablationEndothelial cellsAtherogenesisEnhanced expressionKnockout backgroundVessel wall