2025
Hypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function
Zhang H, de Urturi D, Fernández-Tussy P, Huang Y, Jovin D, Zhang X, Huang S, Lek M, da Silva Catarino J, Sternak M, Citrin K, Swirski F, Gustafsson J, Greif D, Esplugues E, Biwer L, Suárez Y, Fernández-Hernando C. Hypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2417512122. PMID: 40035761, PMCID: PMC11912459, DOI: 10.1073/pnas.2417512122.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsLiver X receptorLesion remodelingMuscle cellsVascular functionArterial media layerContribution of lipid metabolismPhenotypic switchingRegulate vascular toneMonocyte-derived macrophagesLipid metabolismPhenotypic switching of vascular smooth muscle cellsSwitching of vascular smooth muscle cellsNecrotic core areaRegulate vascular functionFoam cell populationVisceral myopathyBladder remodelingAortic atheromaFibrous cap thicknessRemodeling in vivoLipid malabsorptionVascular toneAbundant cell type
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 studies
2019
Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis
Chen PY, Qin L, Li G, Wang Z, Dahlman JE, Malagon-Lopez J, Gujja S, Cilfone N, Kauffman K, Sun L, Sun H, Zhang X, Aryal B, Canfran-Duque A, Liu R, Kusters P, Sehgal A, Jiao Y, Anderson D, Gulcher J, Fernandez-Hernando C, Lutgens E, Schwartz M, Pober J, Chittenden T, Tellides G, Simons M. Endothelial TGF-β signalling drives vascular inflammation and atherosclerosis. Nature Metabolism 2019, 1: 912-926. PMID: 31572976, PMCID: PMC6767930, DOI: 10.1038/s42255-019-0102-3.Peer-Reviewed Original ResearchConceptsTGF-β signalingVascular inflammationDisease progressionPlaque growthProgressive vascular diseaseVessel wall inflammationChronic inflammatory responseSpecific therapeutic interventionsAtherosclerotic plaque growthHyperlipidemic micePlaque inflammationWall inflammationProinflammatory effectsVascular diseaseInflammatory responseVascular permeabilityAtherosclerotic plaquesAbnormal shear stressTherapeutic interventionsInflammationEndothelial TGFΒ signalingVessel wallAtherosclerosisLipid retention
2015
MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels
Goedeke L, Rotllan N, Canfrán-Duque A, Aranda JF, RamÃrez CM, Araldi E, Lin CS, Anderson NN, Wagschal A, de Cabo R, Horton JD, Lasunción MA, Näär AM, Suárez Y, Fernández-Hernando C. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nature Medicine 2015, 21: 1280-1289. PMID: 26437365, PMCID: PMC4711995, DOI: 10.1038/nm.3949.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP Binding Cassette Transporter 1Cholesterol, HDLCholesterol, LDLGene Expression RegulationHep G2 CellsHepatocytesHigh-Throughput Screening AssaysHumansLiverMiceMicroRNAsReceptors, LDLRNA Processing, Post-TranscriptionalSignal TransductionSterol Regulatory Element Binding Protein 1
2011
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos A, Goedeke L, Smibert P, RamÃrez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 9232-9237. PMID: 21576456, PMCID: PMC3107310, DOI: 10.1073/pnas.1102281108.Peer-Reviewed Original ResearchConceptsFatty acid metabolismFatty acid oxidationMiR-33aInsulin receptor substrate 2Sirtuin 6Acid metabolismInsulin-signaling pathwayIntronic microRNAsSterol regulatory element-binding protein 2Acid oxidationHost genesKey enzymeHepatic cell linesMetabolic syndromeCarnitine palmitoyltransferase 1AMetabolic pathwaysSubstrate 2Cellular imbalanceProtein 2Cholesterol homeostasisGenesCell linesLevels of HDLPathwayMetabolism results
2010
Haloperidol disrupts lipid rafts and impairs insulin signaling in SH-SY5Y cells
Sánchez-Wandelmer J, Dávalos A, de la Peña G, Cano S, Giera M, Canfrán-Duque A, Bracher F, MartÃn-Hidalgo A, Fernández-Hernando C, Lasunción M, Busto R. Haloperidol disrupts lipid rafts and impairs insulin signaling in SH-SY5Y cells. Neuroscience 2010, 167: 143-153. PMID: 20123000, DOI: 10.1016/j.neuroscience.2010.01.051.Peer-Reviewed Original ResearchConceptsEffects of haloperidolCholesterol contentLipid raft compositionCholesterol biosynthesisCell cholesterol contentSH-SY5Y cellsNeuroblastoma SH-SY5YHL-60 human cell linesDopamine receptorsMetabolic effectsTherapeutic effectHaloperidolInsulin-Akt signalingImpairs insulinCellular cholesterol homeostasisLipid raftsSH-SY5YFree cholesterolCholesterol homeostasisDependent insulinDrug inhibitionHuman cell linesCell linesPhysiological vehicleInsulin
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