Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/41940
Campo DC Valoridioma
dc.contributor.authorGage, M. C.en_US
dc.contributor.authorBécares, N.en_US
dc.contributor.authorLouie, R.en_US
dc.contributor.authorWaddington, K. E.en_US
dc.contributor.authorZhang, Y.en_US
dc.contributor.authorTittanegro, T. H.en_US
dc.contributor.authorRodríguez-Lorenzo, S.en_US
dc.contributor.authorJathanna, A.en_US
dc.contributor.authorPourcet, B.en_US
dc.contributor.authorPello, O. M.en_US
dc.contributor.authorDe La Rosa, Juan Vladimiren_US
dc.contributor.authorCastrillo, Antonioen_US
dc.contributor.authorPineda-Torra, I.en_US
dc.date.accessioned2018-09-14T12:56:33Z-
dc.date.available2018-09-14T12:56:33Z-
dc.date.issued2018en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10553/41940-
dc.description.abstractMacrophages are key immune cells for the initiation and development of atherosclerotic lesions. However, the macrophage regulatory nodes that determine how lesions progress in response to dietary challenges are not fully understood. Liver X receptors (LXRs) are sterol-regulated transcription factors that play a central role in atherosclerosis by integrating cholesterol homeostasis and immunity. LXR pharmacological activation elicits a robust antiatherosclerotic transcriptional program in macrophages that can be affected by LXRα S196 phosphorylation in vitro. To investigate the impact of these transcriptional changes in atherosclerosis development, we have generated mice carrying a Ser-to-Ala mutation in myeloid cells in the LDL receptor (LDLR)-deficient atherosclerotic background (M-S196ALdlr-KO). M-S196ALdlr-KOmice fed a high-fat diet exhibit increased atherosclerotic plaque burden and lesions with smaller necrotic cores and thinner fibrous caps. These diet-induced phenotypic changes are consistent with a reprogramed macrophage transcriptome promoted by LXRα-S196A during atherosclerosis development. Remarkably, expression of several proliferation-promoting factors, including the protooncogene FoxM1 and its targets, is induced by LXRα-S196A. This is consistent with increased proliferation of plaque-resident cells in M-S196ALdlr-KOmice. Moreover, disrupted LXRα phosphorylation increases expression of phagocytic molecules, resulting in increased apoptotic cell removal by macrophages, explaining the reduced necrotic cores. Finally, the macrophage transcriptome promoted by LXRα-S196A under dietary perturbation is markedly distinct from that revealed by LXR ligand activation, highlighting the singularity of this posttranslational modification. Overall, our findings demonstrate that LXRα phosphorylation at S196 is an important determinant of atherosclerotic plaque development through selective changes in gene transcription that affect multiple pathways.en_US
dc.languageengen_US
dc.publisher0027-8424
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.sourceProceedings of the National Academy of Sciences of the United States of America [ISSN 0027-8424], v. 115, p. E6556-E6565en_US
dc.subject32 Ciencias médicasen_US
dc.subject.otherLiver X receptoren_US
dc.subject.otherAtherosclerosisen_US
dc.subject.otherMacrophagesen_US
dc.subject.otherProliferationen_US
dc.subject.otherFoxM1en_US
dc.titleDisrupting lxrα phosphorylation promotes foxm1 expression and modulates atherosclerosis by inducing macrophage proliferationen_US
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1073/pnas.1721245115
dc.identifier.scopus85049627490
dc.identifier.isi000438050900022-
dc.contributor.authorscopusid24830499600
dc.contributor.authorscopusid37062922900
dc.contributor.authorscopusid57202875127
dc.contributor.authorscopusid56767870000
dc.contributor.authorscopusid35308312500
dc.contributor.authorscopusid57200603654
dc.contributor.authorscopusid57191428883
dc.contributor.authorscopusid57202868259
dc.contributor.authorscopusid14527636000
dc.contributor.authorscopusid11840220100
dc.contributor.authorscopusid55926663500
dc.contributor.authorscopusid55445301000
dc.contributor.authorscopusid7801465530
dc.description.lastpageE6565-
dc.description.firstpageE6556-
dc.relation.volume115-
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.contributor.daisngid618713
dc.contributor.daisngid4172251
dc.contributor.daisngid29552263
dc.contributor.daisngid4557397
dc.contributor.daisngid32313444
dc.contributor.daisngid12657691
dc.contributor.daisngid11856233
dc.contributor.daisngid32328523
dc.contributor.daisngid2142767
dc.contributor.daisngid1295127
dc.contributor.daisngid6668944
dc.contributor.daisngid225640
dc.contributor.daisngid7387206
dc.contributor.wosstandardWOS:Gage, MC
dc.contributor.wosstandardWOS:Becares, N
dc.contributor.wosstandardWOS:Louie, R
dc.contributor.wosstandardWOS:Waddington, KE
dc.contributor.wosstandardWOS:Zhang, Y
dc.contributor.wosstandardWOS:Tittanegro, TH
dc.contributor.wosstandardWOS:Rodriguez-Lorenzo, S
dc.contributor.wosstandardWOS:Jathanna, A
dc.contributor.wosstandardWOS:Pourcet, B
dc.contributor.wosstandardWOS:Pello, OM
dc.contributor.wosstandardWOS:De la Rosa, JV
dc.contributor.wosstandardWOS:Castrillo, A
dc.contributor.wosstandardWOS:Pineda-Torra, I
dc.date.coverdateJulio 2018
dc.identifier.ulpgces
dc.description.sjr5,601
dc.description.jcr9,58
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
dc.description.erihplusERIH PLUS
item.grantfulltextopen-
item.fulltextCon texto completo-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.orcid0000-0003-1443-7548-
crisitem.author.orcid0000-0002-2057-2159-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameDe La Rosa Medina, Juan Vladimir-
crisitem.author.fullNameCastrillo Viguera, Antonio Jesús-
Colección:Artículos
miniatura
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