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dc.contributor.authorFuster, José J 
dc.contributor.authorMacLauchlan, Susan
dc.contributor.authorZuriaga, María A
dc.contributor.authorPolackal, Maya N
dc.contributor.authorOstriker, Allison C
dc.contributor.authorChakraborty, Raja
dc.contributor.authorWu, Chia-Ling
dc.contributor.authorSano, Soichi
dc.contributor.authorMuralidharan, Sujatha
dc.contributor.authorRius, Cristina 
dc.contributor.authorVuong, Jacqueline
dc.contributor.authorJacob, Sophia
dc.contributor.authorMuralidhar, Varsha
dc.contributor.authorRobertson, Avril A B
dc.contributor.authorCooper, Matthew A
dc.contributor.authorAndres, Vicente 
dc.contributor.authorHirschi, Karen K
dc.contributor.authorMartin, Kathleen A
dc.contributor.authorWalsh, Kenneth
dc.date.accessioned2020-04-22T15:26:32Z
dc.date.available2020-04-22T15:26:32Z
dc.date.issued2017-02
dc.identifier.citationScience. 2017; 355(6327):842-847es_ES
dc.identifier.issn0036-8075es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9683
dc.description.abstractHuman aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This clonal hematopoiesis correlates with an increased risk of atherosclerotic cardiovascular disease. We studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome-mediated interleukin-1β secretion. An NLRP3 inhibitor showed greater atheroprotective activity in chimeric mice reconstituted with TET2-deficient cells than in nonchimeric mice. These results support the hypothesis that somatic TET2 mutations in blood cells play a causal role in atherosclerosis.es_ES
dc.description.sponsorshipJ.J.F. is supported by American Heart Association-Scientist Development Grant 17SDG33400213. K.W. is supported by NIH grants HL132564, HL126141, and HL131006. K.A.M. is supported by NIH grants HL119529 and HL118430. The CNIC is supported by the Ministerio de Economia, Industria y Competitividad (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). M.A.C. is a cofounder of Inflazome, a company developing drugs that target inflammasomes. J.J.F. and K.W. are coinventors on patent application 62/368,338 submitted by Boston University that is related to the treatment of cardiometabolic diseases associated with TET2 somatic mutations. Data reported in this paper were deposited into the National Center for Biotechnology Information Gene Expression Omnibus with accession numbers GSE81398 and GSE89824.es_ES
dc.language.isoenges_ES
dc.publisherAAASes_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshAtherosclerosis es_ES
dc.subject.meshDNA-Binding Proteins es_ES
dc.subject.meshHematopoiesis es_ES
dc.subject.meshHematopoietic Stem Cells es_ES
dc.subject.meshInflammasomes es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMutation es_ES
dc.subject.meshNLR Family, Pyrin Domain-Containing 3 Protein es_ES
dc.subject.meshPlaque, Atherosclerotices_ES
dc.subject.meshProto-Oncogene Proteins es_ES
dc.subject.meshReceptors, LDLes_ES
dc.titleClonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in micees_ES
dc.typeArtículoes_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID28104796es_ES
dc.format.volume355es_ES
dc.format.number6327es_ES
dc.format.page842-847es_ES
dc.identifier.doi10.1126/science.aag1381es_ES
dc.contributor.funderAmerican Heart Associationes_ES
dc.contributor.funderNational Institutes of Health (United States)es_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)es_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1095-9203es_ES
dc.relation.publisherversionhttps://doi.org/10.1126/science.aag1381es_ES
dc.identifier.journalScience (New York, N.Y.)es_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional