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dc.contributor.authorZotes, Teresa M
dc.contributor.authorArias, Cristina F
dc.contributor.authorFuster, Jose J. 
dc.contributor.authorSpada, Roberto
dc.contributor.authorPérez-Yagüe, Sonia
dc.contributor.authorHirsch, Emilio
dc.contributor.authorWymann, Matthias
dc.contributor.authorCarrera, Ana C
dc.contributor.authorAndres, Vicente 
dc.contributor.authorBarber, Domingo F
dc.date.accessioned2019-05-07T11:08:51Z
dc.date.available2019-05-07T11:08:51Z
dc.date.issued2013
dc.identifier.citationPLoS One. 2013; 8(8):e72674es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7546
dc.description.abstractAtherosclerosis is an inflammatory disease regulated by infiltrating monocytes and T cells, among other cell types. Macrophage recruitment to atherosclerotic lesions is controlled by monocyte infiltration into plaques. Once in the lesion, macrophage proliferation in situ, apoptosis, and differentiation to an inflammatory (M1) or anti-inflammatory phenotype (M2) are involved in progression to advanced atherosclerotic lesions. We studied the role of phosphoinositol-3-kinase (PI3K) p110γ in the regulation of in situ apoptosis, macrophage proliferation and polarization towards M1 or M2 phenotypes in atherosclerotic lesions. We analyzed atherosclerosis development in LDLR(-/-)p110γ(+/-) and LDLR(-/-)p110γ(-/-) mice, and performed expression and functional assays in tissues and primary cells from these and from p110γ(+/-) and p110γ(-/-) mice. Lack of p110γ in LDLR(-/-) mice reduces the atherosclerosis burden. Atherosclerotic lesions in fat-fed LDLR(-/-)p110γ(-/-) mice were smaller than in LDLR(-/-)p110γ(+/-) controls, which coincided with decreased macrophage proliferation in LDLR(-/-)p110γ(-/-) mouse lesions. This proliferation defect was also observed in p110γ(-/-) bone marrow-derived macrophages (BMM) stimulated with macrophage colony-stimulating factor (M-CSF), and was associated with higher intracellular cyclic adenosine monophosphate (cAMP) levels. In contrast, T cell proliferation was unaffected in LDLR(-/-)p110γ(-/-) mice. Moreover, p110γ deficiency did not affect macrophage polarization towards the M1 or M2 phenotypes or apoptosis in atherosclerotic plaques, or polarization in cultured BMM. Our results suggest that higher cAMP levels and the ensuing inhibition of macrophage proliferation contribute to atheroprotection in LDLR(-/-) mice lacking p110γ. Nonetheless, p110γ deletion does not appear to be involved in apoptosis, in macrophage polarization or in T cell proliferation.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Science and Innovation (SAF-2007-60498, SAF-2008-00471, SAF-2011-23639 to DFB, SAF201016044 to VA, AP2007-01711 to TMZ, BES-2009-016547 to RS), the Research Network in Inflammation and Rheumatic Diseases (RIER) of the ISCIII-MSPS Cooperative Research Thematic Network program (RD08/0075/0015 to DFB), the Madrid Regional Government (200520M040 to DFB) and the Thematic Research Network in Cardiovascular Diseases (RECAVA; RD06/0014/0021 to VA).es_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshApoptosis es_ES
dc.subject.meshAtherosclerosis es_ES
dc.subject.meshClass Ib Phosphatidylinositol 3-Kinase es_ES
dc.subject.meshCyclic AMP es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshReceptors, LDL es_ES
dc.subject.meshCell Proliferation es_ES
dc.titlePI3K p110γ deletion attenuates murine atherosclerosis by reducing macrophage proliferation but not polarization or apoptosis in lesionses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID23991137es_ES
dc.format.volume8es_ES
dc.format.number8es_ES
dc.format.pagee72674es_ES
dc.identifier.doi10.1371/journal.pone.0072674es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderComunidad de Madrides_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0072674es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF-2007-60498es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF-2008-00471es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF-2011-23639es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF-2010-16044es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2009-016547es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD08/0075/0015es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD06/0014/0021es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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