2026-07-21T14:57:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/96832024-09-27T08:20:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Fuster, José J
author
MacLauchlan, Susan
author
Zuriaga, María A
author
Polackal, Maya N
author
Ostriker, Allison C
author
Chakraborty, Raja
author
Wu, Chia-Ling
author
Sano, Soichi
author
Muralidharan, Sujatha
author
Rius, Cristina
author
Vuong, Jacqueline
author
Jacob, Sophia
author
Muralidhar, Varsha
author
Robertson, Avril A B
author
Cooper, Matthew A
author
Andres, Vicente
author
Hirschi, Karen K
author
Martin, Kathleen A
author
Walsh, Kenneth
funder
American Heart Association
funder
National Institutes of Health (Estados Unidos)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Fundación ProCNIC
2020-04-22T15:26:32Z
2020-04-22T15:26:32Z
2017-02
Science. 2017; 355(6327):842-847
10.1126/science.aag1381
1095-9203
0036-8075
Science (New York, N.Y.)
28104796
http://hdl.handle.net/20.500.12105/9683
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.
eng
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
journal article
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