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dc.contributor.author | Fuster, José J | |
dc.contributor.author | MacLauchlan, Susan | |
dc.contributor.author | Zuriaga, María A | |
dc.contributor.author | Polackal, Maya N | |
dc.contributor.author | Ostriker, Allison C | |
dc.contributor.author | Chakraborty, Raja | |
dc.contributor.author | Wu, Chia-Ling | |
dc.contributor.author | Sano, Soichi | |
dc.contributor.author | Muralidharan, Sujatha | |
dc.contributor.author | Rius, Cristina | |
dc.contributor.author | Vuong, Jacqueline | |
dc.contributor.author | Jacob, Sophia | |
dc.contributor.author | Muralidhar, Varsha | |
dc.contributor.author | Robertson, Avril A B | |
dc.contributor.author | Cooper, Matthew A | |
dc.contributor.author | Andres, Vicente | |
dc.contributor.author | Hirschi, Karen K | |
dc.contributor.author | Martin, Kathleen A | |
dc.contributor.author | Walsh, Kenneth | |
dc.date.accessioned | 2020-04-22T15:26:32Z | |
dc.date.available | 2020-04-22T15:26:32Z | |
dc.date.issued | 2017-02 | |
dc.identifier.citation | Science. 2017; 355(6327):842-847 | es_ES |
dc.identifier.issn | 0036-8075 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9683 | |
dc.description.abstract | Human 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.sponsorship | J.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.iso | eng | es_ES |
dc.publisher | American Association for the Advancement of Science (AAAS) | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Atherosclerosis | es_ES |
dc.subject.mesh | DNA-Binding Proteins | es_ES |
dc.subject.mesh | Hematopoiesis | es_ES |
dc.subject.mesh | Hematopoietic Stem Cells | es_ES |
dc.subject.mesh | Inflammasomes | es_ES |
dc.subject.mesh | Macrophages | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Mutation | es_ES |
dc.subject.mesh | NLR Family, Pyrin Domain-Containing 3 Protein | es_ES |
dc.subject.mesh | Plaque, Atherosclerotic | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins | es_ES |
dc.subject.mesh | Receptors, LDL | es_ES |
dc.title | Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 28104796 | es_ES |
dc.format.volume | 355 | es_ES |
dc.format.number | 6327 | es_ES |
dc.format.page | 842-847 | es_ES |
dc.identifier.doi | 10.1126/science.aag1381 | es_ES |
dc.contributor.funder | American Heart Association | |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1095-9203 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1126/science.aag1381 | es_ES |
dc.identifier.journal | Science (New York, N.Y.) | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |