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dc.contributor.authordel Monte, Alberto 
dc.contributor.authorArroyo, Ana B.
dc.contributor.authorAndres-Manzano, Maria J. 
dc.contributor.authorGarcia-Barbera, Nuria
dc.contributor.authorCaleprico, Maria S. 
dc.contributor.authorVicente, Vicente
dc.contributor.authorRoldan, Vanessa
dc.contributor.authorGonzalez-Conejero, Rocio
dc.contributor.authorMartinez, Constantino
dc.contributor.authorAndres, Vicente 
dc.date.accessioned2018-11-05T11:58:21Z
dc.date.available2018-11-05T11:58:21Z
dc.date.issued2018
dc.identifierISI:000435424900064
dc.identifier.citationPLoS One. 2018; 13(6):e0198932
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6577
dc.description.abstractBackground Atherosclerosis involves activation of the IRAK1/TRAF6/NF-kappa B inflammatory cascade, which is negatively regulated by miR146a. Previous studies showed that the TT genotype of rs2431697, located near the miR-146a gene, drives lower miR-146a transcription and predicts adverse cardiovascular events in anticoagulated atrial fibrillation patients. Moreover, systemic miR-146a administration protects mice from atherosclerosis. Here we evaluated the ability of miR-146a expression in the hematopoietic component to regulate atherosclerosis in low-density lipoprotein receptor-null mice (LdIr(-/-)). Methods and results Lethally-irradiated LdIr(-/-)mice transplanted with bone marrow from wild-type or miR-146a-null mice were fed an atherogenic diet for 8 and 20 weeks. Irak1, Traf6 and MIR146A expression were quantified in thoracic aorta by qRT-PCR and Western blot. Aortic plaque size and composition were characterized by Oil-Red staining and immunohistochemistry and leukocyte recruitment by intravital microscopy. Blood cell counts were similar in fat-fed Ldir(-/-)mice with or without hematopoietic miR-146a expression. However, plasma cholesterol decreased in fat-fed Ldir(-/-)mice transplanted with bone marrow deficient for miR-146a. Finally, aortic atherosclerosis burden and recruitment of leukocytes into the vessel wall were undistinguishable between the two groups, despite higher levels of Irak1 and Traf6 mRNA and protein in the aorta of fat-fed mice lacking hematopoietic miR-146a expression. Conclusions miR-146a deficiency exclusively in hematopoietic cells modulates cholesterol levels in plasma and the expression of its targets in the artery wall of fat-fed LdIr(-/-)mice, but does not 16 accelerate atherosclerosis. Atheroprotection upon systemic miR-146a administration may therefore be caused by specific effects on vascular cells.
dc.description.sponsorshipThis study was supported by research grants from the Institute de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) [PI14/00253, Red RIC (RD12/0042/0050 and RD12/0042/0028), CIBERCV CB16/11/00405] and 19873/GERM/15 (Fundacion Seneca). A.D.M. has a predoctoral contract from the Spanish Ministerio de Economia, lndustria y Competitividad (MEIC) (BES-2014-06779) and A.B.A. has a research fellowship from Sociedad Espanola de Trombosis y Hemostasia (SETH). The CNIC is supported by the Ministerio de Economia, Industria y Competitividad (MEIC) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSYSTEMIC-LUPUS-ERYTHEMATOSUS
dc.subjectMICRORNAS
dc.subjectMICE
dc.subjectMACROPHAGES
dc.subjectINFLAMMATION
dc.subjectINHIBITION
dc.subjectACTIVATION
dc.subjectEXPRESSION
dc.subjectPROTECTS
dc.subjectBIOLOGY
dc.titlemiR-146a deficiency in hematopoietic cells is not involved in the development of atherosclerosis
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29902229
dc.format.volume13
dc.identifier.doi10.1371/journal.pone.0198932
dc.contributor.funderInstituto de Salud Carlos III - ISCIII
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)
dc.contributor.funderFundación Seneca
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderSociedad Espanola de Trombosis y Hemostasia
dc.contributor.funderFundación ProCNIC
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0198932
dc.identifier.journalPLoS ONE
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/00253es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0050es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0028es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00405es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2014-06779es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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