2021
Gene Expression Signature in Patients With Symptomatic Peripheral Artery Disease
Newman JD, Cornwell MG, Zhou H, Rockman C, Heguy A, Suarez Y, Cheng HS, Feinberg MW, Hochman JS, Ruggles KV, Berger JS. Gene Expression Signature in Patients With Symptomatic Peripheral Artery Disease. Arteriosclerosis Thrombosis And Vascular Biology 2021, 41: 1521-1533. PMID: 33657880, PMCID: PMC8048111, DOI: 10.1161/atvbaha.120.315857.Peer-Reviewed Original Research
2020
Cav-1 (Caveolin-1) Deficiency Increases Autophagy in the Endothelium and Attenuates Vascular Inflammation and Atherosclerosis
Zhang X, Ramírez CM, Aryal B, Madrigal-Matute J, Liu X, Diaz A, Torrecilla-Parra M, Suárez Y, Cuervo AM, Sessa WC, Fernández-Hernando C. Cav-1 (Caveolin-1) Deficiency Increases Autophagy in the Endothelium and Attenuates Vascular Inflammation and Atherosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 1510-1522. PMID: 32349535, PMCID: PMC7253189, DOI: 10.1161/atvbaha.120.314291.Peer-Reviewed Original ResearchConceptsCav-1 deficiencyCav-1-deficient miceCav-1Autophagic fluxCholesterol-rich membrane domainsCav-1 interactsATG5-ATG12 complexEndothelial Cav-1 expressionRegulation of autophagyNovel molecular mechanismExtracellular matrix remodelingAutophagosome componentsMembrane domainsLipid raftsAutophagosome formationPlasma membraneCav-1 expressionMolecular mechanismsLDL transcytosisCellular localizationImportant regulatorAutophagyAutophagy contributesRelevant regulatorMatrix remodeling
2019
Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation
Ramírez CM, Zhang X, Bandyopadhyay C, Rotllan N, Sugiyama MG, Aryal B, Liu X, He S, Kraehling JR, Ulrich V, Lin CS, Velazquez H, Lasunción MA, Li G, Suárez Y, Tellides G, Swirski FK, Lee WL, Schwartz MA, Sessa WC, Fernández-Hernando C. Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation. Circulation 2019, 140: 225-239. PMID: 31154825, PMCID: PMC6778687, DOI: 10.1161/circulationaha.118.038571.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseDiet-induced atherosclerosisNO productionVascular inflammationENOS activationEndothelial nitric oxide synthase activationNitric oxide synthase activationAthero-protective functionsLipid metabolic factorsEndothelial cell inflammationNitric oxide synthaseWild-type miceMice Lacking ExpressionProduction of NOExtracellular matrix remodelingInflammatory primingHyperlipidemic miceInflammatory pathwaysAortic archCell inflammationOxide synthaseMetabolic factorsMouse modelAtherosclerosisInflammation
2018
Inhibition of profibrotic microRNA-21 affects platelets and their releasate
Barwari T, Eminaga S, Mayr U, Lu R, Armstrong PC, Chan MV, Sahraei M, Fernández-Fuertes M, Moreau T, Barallobre-Barreiro J, Lynch M, Yin X, Schulte C, Baig F, Pechlaner R, Langley SR, Zampetaki A, Santer P, Weger M, Plasenzotti R, Schosserer M, Grillari J, Kiechl S, Willeit J, Shah AM, Ghevaert C, Warner TD, Fernández-Hernando C, Suárez Y, Mayr M. Inhibition of profibrotic microRNA-21 affects platelets and their releasate. JCI Insight 2018, 3: e123335. PMID: 30385722, PMCID: PMC6238735, DOI: 10.1172/jci.insight.123335.Peer-Reviewed Original ResearchConceptsMiR-21 inhibitionMiR-21TGF-β1TGF-β1 secretionMiR-21 levelsMiR-21 mimicsMiR-21 inhibitorMurine cardiac fibroblastsBruneck StudyLow plateletsAntifibrotic effectsProfibrotic factorsLeukocyte countSpecific therapyClinical trialsOrgan diseaseTGF-β1 releaseLittermate controlsBone marrowCardiac fibroblastsMegakaryocyte numberMouse heartsFibrosisPlasma samplesPlatelet release
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 diseaseLanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages
Araldi E, Fernández-Fuertes M, Canfrán-Duque A, Tang W, Cline GW, Madrigal-Matute J, Pober JS, Lasunción MA, Wu D, Fernández-Hernando C, Suárez Y. Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages. Cell Reports 2017, 19: 2743-2755. PMID: 28658622, PMCID: PMC5553565, DOI: 10.1016/j.celrep.2017.05.093.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Activator of transcriptionCholesterol biosynthetic pathwayTranscriptional repressionBiosynthetic pathwayLanosterol accumulationGene productsSterol intermediatesSignal transducerGene expressionSelective regulatorSTAT2 activationInnate immune responseType I interferonConditional disruptionCritical functionsMembrane fluidityROS productionMacrophage immunityListeria monocytogenes infectionResistance of miceMouse macrophagesInnate immunityI interferonCYP51A1
2016
Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease
Montenont E, Echagarruga C, Allen N, Araldi E, Suarez Y, Berger JS. Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease. Blood 2016, 128: 2033-2042. PMID: 27609643, PMCID: PMC5073182, DOI: 10.1182/blood-2016-03-703157.Peer-Reviewed Original ResearchConceptsPlatelet activityCardiovascular diseaseMEG-01 cellsHyperreactive platelet phenotypeBasal intracellular calcium concentrationPathogenesis of atherothrombosisSex-matched controlsIntracellular calcium concentrationMessenger RNAMEG-01Healthy controlsClinical significancePlatelet-related genesPlatelet phenotypeBasal stateMegakaryoblastic cell line MEG-01Human megakaryoblastic cell line MEG-01Thrombin activationDiseaseCalcium concentrationKD phenotypeProtein levelsF-actin contentPlatelet messenger RNAPlatelet RNA
2015
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Haskins JW, Zhang S, Means RE, Kelleher JK, Cline GW, Canfrán-Duque A, Suárez Y, Stern DF. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science Signaling 2015, 8: ra111. PMID: 26535009, PMCID: PMC4666504, DOI: 10.1126/scisignal.aac5124.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNeuregulin-1Proto-Oncogene Proteins c-aktReceptor, ErbB-4Receptors, LDLSterol Regulatory Element Binding Protein 2TOR Serine-Threonine KinasesConceptsIntracellular domainEGFR family membersLow-density lipoprotein uptakeCholesterol biosynthesisSREBP target genesRapamycin complex 1ErbB4 intracellular domainSite-1 proteaseCholesterol biosynthesis genesSoluble intracellular domainCholesterol biosynthetic pathwayActivation of ErbB4Mammary epithelial cellsInhibition of AktSterol regulatory elementBiosynthesis genesLipoprotein uptakeRegulatory elementsBiosynthetic pathwayTarget genesDevelopmental processesMetabolic remodelingMature formNeuregulin-1Cellular membranes
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
2006
Vitamin D regulates the phenotype of human breast cancer cells
Pendás-Franco N, González-Sancho J, Suárez Y, Aguilera O, Steinmeyer A, Gamallo C, Berciano MT, Lafarga M, Muñoz A. Vitamin D regulates the phenotype of human breast cancer cells. Differentiation 2006, 75: 193-207. PMID: 17288543, DOI: 10.1111/j.1432-0436.2006.00131.x.Peer-Reviewed Original ResearchConceptsSmooth muscle alpha-actinFocal adhesion kinaseBreast cancer cellsHuman breast cancer cellsCancer cellsP-cadherinFocal adhesion plaquesMDA-MB-453Muscle alpha-actinMesenchymal markers N-cadherinMDA-MB-468 cellsAdhesion kinasePlasma membraneAdhesion plaquesMDA-MB-453 cellsLarge cytoplasmic extensionsActin filamentsE-cadherin expressionCell adhesionCell typesN-cadherinAlpha-actinBreast cancer cell linesCancer cell linesLaser confocal
2004
JNK activation is critical for Aplidin™-induced apoptosis
Cuadrado A, González L, Suárez Y, Martínez T, Muñoz A. JNK activation is critical for Aplidin™-induced apoptosis. Oncogene 2004, 23: 4673-4680. PMID: 15122339, DOI: 10.1038/sj.onc.1207636.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsApoptosisBlotting, WesternBreast NeoplasmsCell DivisionCell Line, TumorCell SurvivalDepsipeptidesEnzyme ActivationFemaleFibroblastsHumansMitogen-Activated Protein KinasesNF-kappa BPeptides, CyclicPhosphorylationPrecipitin TestsProto-Oncogene Proteins c-junTranscription Factor AP-1
2003
Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells.
Suárez Y, González L, Cuadrado A, Berciano M, Lafarga M, Muñoz A. Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells. Molecular Cancer Therapeutics 2003, 2: 863-72. PMID: 14555705.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesApoptosisBreast NeoplasmsCaspase InhibitorsCaspasesCell CycleCell NucleusCell Transformation, NeoplasticCysteine Proteinase InhibitorsDepsipeptidesFemaleFlow CytometryHumansLysosomesMaleMollusk VenomsOligopeptidesPeptidesProstatic NeoplasmsTumor Cells, CulturedConceptsAnti-apoptotic Bcl-2 proteinGeneral caspase inhibitorSevere cytoplasmic swellingMitochondrial membrane potentialCell cycle arrestBcl-2 proteinKahalalide FTranslation inhibitorsMarine-derived compoundsNuclear domainsCaspase inhibitorsNuclear envelopeNew marine-derived compoundDNA degradationEndoplasmic reticulumHuman cellsCell deathNovel antitumor drugsBreast cancer cellsJC-1LysoTracker GreenCell nucleiBreast cancer cell linesCancer cell linesMitochondrial damage
2002
A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease
Castillo S, Reyes G, Tejedor D, Mozas P, Suarez Y, Lasuncion M, Cenarro A, Civeira F, Alonso R, Mata P, Pocovi M, Group of FH O. A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease. Human Mutation 2002, 20: 477-477. PMID: 12442279, DOI: 10.1002/humu.9087.Peer-Reviewed Original ResearchConceptsDouble mutant alleleLDL receptor geneFamilial hypercholesterolemiaHomozygous patientsReceptor geneSpanish FH patientsCholesterol-lowering treatmentLDL cholesterol reductionPlasma cholesterol levelsAbility of LDLMitogen-stimulated lymphocytesCholesterol levelsCholesterol reductionFH patientsCardiovascular diseasePatientsHomozygous FHHeterozygous patientsUnrelated patientsCytometric analysisHypercholesterolemiaLDL bindingDefective LDL bindingCell proliferationGenetic disordersAplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*
Cuadrado A, Garcı́a-Fernández L, González L, Suárez Y, Losada A, Alcaide V, Martı́nez T, Fernández-Sousa J, Sánchez-Puelles J, Muñoz A. AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*. Journal Of Biological Chemistry 2002, 278: 241-250. PMID: 12414812, DOI: 10.1074/jbc.m201010200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCell DivisionCell SurvivalCells, CulturedDepsipeptidesEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFemaleFibroblastsFlow CytometryGlutathioneHumansJNK Mitogen-Activated Protein KinasesKidney NeoplasmsMiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPeptides, CyclicPhosphorylationProto-Oncogene Proteins pp60(c-src)Receptors, Platelet-Derived Growth FactorTumor Cells, CulturedConceptsEpidermal growth factor receptorP38 MAPK activationP38 MAPKNon-receptor protein tyrosine kinase SrcGrowth factor receptorMAPK activationProtein tyrosine kinase SrcStress response programSustained activationFactor receptorCancer cellsMDA-MB-231 breast cancer cellsHuman cancer cellsBenzyloxycarbonyl-VADKinase SrcHuman MDA-MB-231 breast cancer cellsMDA-MB-231 cellsMolecular basisKinase JNKPretreatment of cellsMouse embryosEGFR activationFluoromethyl ketoneGrowth arrestHuman renal cancer