Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/72765
DC FieldValueLanguage
dc.contributor.authorLouie, R.en_US
dc.contributor.authorGage, M.en_US
dc.contributor.authorPatel, A.en_US
dc.contributor.authorYona, S.en_US
dc.contributor.authorCastrillo, A.en_US
dc.contributor.authorPineda-Torra, I.en_US
dc.date.accessioned2020-05-26T09:56:02Z-
dc.date.available2020-05-26T09:56:02Z-
dc.date.issued2019en_US
dc.identifier.issn0021-9150en_US
dc.identifier.otherWoS-
dc.identifier.urihttp://hdl.handle.net/10553/72765-
dc.description.abstractBackground: IRF8 is a haematopoietic transcription factor crucial for the development of myeloid cells and known to mediate their inflammatory responses. Our group has previously shown IRF8 to selectively modulate the expression of macrophage genes involved in atherosclerotic plaque development. Aim: To investigate the role of myeloid-IRF8 in atherosclerosis development. Methods: We have generated a myeloid-IRF8 deficient mouse model, using the LysM directed Cre recombinase, on the LDLR-deficient background (M-IRF8KOLdlrKO). Mice were challenged with a western diet for 12 weeks after which atherosclerotic lesions were quantified in the aortic root by H&E staining respectively. Results: Plaque coverage in the aortic roots was significantly higher in WTLdlrKO mice compared to M-IRF8KOLdlrKO (20.53 ±0.27% vs 12.83 ±0.27%, P=0.04). Interestingly, M-IRF8KOLdlrKO mice display decreased expression of pro-atherosclerotic genes Cyp27a1, Cxcl16 and iNOS in bone marrow-derived macrophages, via quantitative PCR. Among these, we demonstrated that Cyp27a1, involved in lipid metabolism, inflammation and leukocyte migration, harbours a novel IRF8 binding site by chromatin immunoprecipitation assays and is remarkably reduced in IRF8-deficient macrophages at both mRNA (70% decrease) and protein level, shown via western blots. Furthermore, recent RNA-Seq analysis on the basal bone derived macrophages have highlighted 167 differential upregulated genes and 199 differential downregulated genes. Conclusions: Overall, this suggests myeloid-IRF8 deficiency confers protection against atherosclerosis. Interestingly, myeloid-IRF8 regulates the expression of many genes including those involved in inflammation and lipid homeostasis (catabolism via Cyp27a1 and uptake via Cxcl16). These processes are critical in the development of the atherosclerotic plaque.en_US
dc.languageengen_US
dc.relation.ispartofAtherosclerosisen_US
dc.sourceAtherosclerosis [ISSN 0021-9150], v. 287, p. E18-E19, (Agosto 2019)en_US
dc.subject32 Ciencias médicasen_US
dc.titleMyeloid Interferon Regulatory Factor 8 Deficiency Prevents The Development Of Atherosclerosisen_US
dc.typeinfo:eu-repo/semantics/conferenceObjecten_US
dc.typeConferenceObjecten_US
dc.relation.conference87th Congress of the European-Atherosclerosis-Society (EAS)en_US
dc.identifier.doi10.1016/j.atherosclerosis.2019.06.052en_US
dc.identifier.isi000482110800052-
dc.identifier.eissn1879-1484-
dc.description.lastpageE19en_US
dc.description.firstpageE18en_US
dc.relation.volume287en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Actas de congresosen_US
dc.contributor.daisngid29552263-
dc.contributor.daisngid618713-
dc.contributor.daisngid12906816-
dc.contributor.daisngid15550640-
dc.contributor.daisngid225640-
dc.contributor.daisngid31482455-
dc.description.numberofpages2en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:Louie, R-
dc.contributor.wosstandardWOS:Gage, M-
dc.contributor.wosstandardWOS:Patel, A-
dc.contributor.wosstandardWOS:Yona, S-
dc.contributor.wosstandardWOS:Castrillo, A-
dc.contributor.wosstandardWOS:Pineda-Torra, I-
dc.date.coverdateAgosto 2019en_US
dc.identifier.conferenceidevents121164-
dc.identifier.ulpgces
dc.description.sjr1,515
dc.description.jcr3,919
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
item.grantfulltextnone-
item.fulltextSin texto completo-
crisitem.event.eventsstartdate26-05-2019-
crisitem.event.eventsenddate29-05-2019-
Appears in Collections:Actas de congresos
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