{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:02:49Z","timestamp":1790834569492,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T00:00:00Z","timestamp":1377129600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0072674","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T21:26:22Z","timestamp":1377206782000},"page":"e72674","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["PI3K p110\u03b3 Deletion Attenuates Murine Atherosclerosis by Reducing Macrophage Proliferation but Not Polarization or Apoptosis in Lesions"],"prefix":"10.1371","volume":"8","author":[{"given":"Teresa M.","family":"Zotes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina F.","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 J.","family":"Fuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Spada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"P\u00e9rez-Yag\u00fce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Wymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Carrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingo F.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,8,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nri1882","article-title":"The immune response in atherosclerosis: a double-edged sword","volume":"6","author":"GK Hansson","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.immunol.021908.132620","article-title":"Immune and inflammatory mechanisms of atherosclerosis (*)","volume":"27","author":"E Galkina","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"AJ Lusis","year":"2000","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1006\/clim.1998.4682","article-title":"Are immunological mechanisms relevant for the development of atherosclerosis?","volume":"90","author":"JL Witztum","year":"1999","journal-title":"Clin Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.2538","article-title":"Atherosclerosis: current pathogenesis and therapeutic options","volume":"17","author":"C Weber","year":"2011","journal-title":"Nat Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"e779","DOI":"10.1371\/journal.pone.0000779","article-title":"Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions","volume":"2","author":"OJ de Boer","year":"2007","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2011.04.005","article-title":"Macrophages in the pathogenesis of atherosclerosis","volume":"145","author":"KJ Moore","year":"2011","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1161\/ATVBAHA.107.161174","article-title":"Chemokines in atherosclerosis: an update","volume":"28","author":"A Zernecke","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nri1733","article-title":"Monocyte and macrophage heterogeneity","volume":"5","author":"S Gordon","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/jlb.43.2.148","article-title":"Comparison of bone marrow progenitors responsive to granulocyte-macrophage colony stimulating factor and macrophage colony stimulating factor-1","volume":"43","author":"LA Falk","year":"1988","journal-title":"J Leukoc Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nri2356","article-title":"Colony-stimulating factors in inflammation and autoimmunity","volume":"8","author":"JA Hamilton","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/MOL.0b013e3283309848","article-title":"Macrophage heterogeneity in atherosclerotic plaques","volume":"20","author":"JL Johnson","year":"2009","journal-title":"Curr Opin Lipidol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e8852","DOI":"10.1371\/journal.pone.0008852","article-title":"Macrophage plasticity in experimental atherosclerosis","volume":"5","author":"J Khallou-Laschet","year":"2010","journal-title":"PLoS One"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1172\/JCI119480","article-title":"Aortic endothelial cells regulate proliferation of human monocytes in vitro via a mechanism synergistic with macrophage colony-stimulating factor. Convergence at the cyclin E\/p27(Kip1) regulatory checkpoint","volume":"99","author":"AS Antonov","year":"1997","journal-title":"J Clin Invest"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/00041433-200010000-00008","article-title":"Macrophage proliferation in atherosclerosis","volume":"11","author":"M Sakai","year":"2000","journal-title":"Curr Opin Lipidol"},{"key":"ref16","doi-asserted-by":"crossref","DOI":"10.1194\/jlr.R800032-JLR200","article-title":"Mechanisms and consequences of macrophage apoptosis in atherosclerosis","volume":"50","author":"T Seimon","year":"2009","journal-title":"J Lipid Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.5551\/jat1994.7.14","article-title":"Granulocyte\/macrophage colony-stimulating factor plays an essential role in oxidized low density lipoprotein-induced macrophage proliferation","volume":"7","author":"T Biwa","year":"2000","journal-title":"J Atheroscler Thromb"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/344254a0","article-title":"Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins","volume":"344","author":"TB Rajavashisth","year":"1990","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.2337\/diabetes.53.12.3217","article-title":"Hyperlipidemia in concert with hyperglycemia stimulates the proliferation of macrophages in atherosclerotic lesions: potential role of glucose-oxidized LDL","volume":"53","author":"N Lamharzi","year":"2004","journal-title":"Diabetes"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5810","DOI":"10.1074\/jbc.275.8.5810","article-title":"Sites of action of protein kinase C and phosphatidylinositol 3-kinase are distinct in oxidized low density lipoprotein-induced macrophage proliferation","volume":"275","author":"T Biwa","year":"2000","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"8077","DOI":"10.1073\/pnas.0702663104","article-title":"Deletion of the phosphoinositide 3-kinase p110gamma gene attenuates murine atherosclerosis","volume":"104","author":"JD Chang","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/342699a0","article-title":"The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase","volume":"342","author":"L Varticovski","year":"1989","journal-title":"Nature"},{"key":"ref23","first-page":"26393","article-title":"Macrophage colony-stimulating factor promotes cell survival through Akt\/protein kinase B. J Biol Chem","volume":"274","author":"TW Kelley","year":"1999"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"10380","DOI":"10.1074\/jbc.270.18.10380","article-title":"Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3-kinase to Grb2.Sos complexes in human monocytes","volume":"270","author":"A Saleem","year":"1995","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tibs.2005.02.008","article-title":"Signalling by PI3K isoforms: insights from gene-targeted mice","volume":"30","author":"B Vanhaesebroeck","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1126\/science.287.5455.1040","article-title":"Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration","volume":"287","author":"T Sasaki","year":"2000","journal-title":"Science"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"589","DOI":"10.4049\/jimmunol.176.1.589","article-title":"Class IB-phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PI3K-induced systemic lupus but not T cell invasion","volume":"176","author":"DF Barber","year":"2006","journal-title":"J Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.4049\/jimmunol.180.4.2081","article-title":"Selective regulation of CD8 effector T cell migration by the p110 gamma isoform of phosphatidylinositol 3-kinase","volume":"180","author":"AL Martin","year":"2008","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1161\/CIRCULATIONAHA.107.720466","article-title":"Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes","volume":"117","author":"A Fougerat","year":"2008","journal-title":"Circulation"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0014-4827(03)00318-5","article-title":"Requirement for PI 3-kinase gamma in macrophage migration to MCP-1 and CSF-1","volume":"290","author":"GE Jones","year":"2003","journal-title":"Exp Cell Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.cellsig.2005.02.002","article-title":"M-CSF stimulated differentiation requires persistent MEK activity and MAPK phosphorylation independent of Grb2-Sos association and phosphatidylinositol 3-kinase activity","volume":"17","author":"S Gobert Gosse","year":"2005","journal-title":"Cell Signal"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2004.07.017","article-title":"PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects","volume":"118","author":"E Patrucco","year":"2004","journal-title":"Cell"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"9977","DOI":"10.1074\/jbc.M512502200","article-title":"Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B","volume":"281","author":"P Voigt","year":"2006","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neuroscience.2012.12.036","article-title":"Phosphoinositide 3-kinase gamma mediates microglial phagocytosis via lipid kinase-independent control of cAMP","volume":"233","author":"C Schmidt","year":"2013","journal-title":"Neuroscience"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.4049\/jimmunol.163.8.4140","article-title":"Adenosine inhibits macrophage colony-stimulating factor-dependent proliferation of macrophages through the induction of p27kip-1 expression","volume":"163","author":"J Xaus","year":"1999","journal-title":"J Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"17475","DOI":"10.1073\/pnas.0908641106","article-title":"A CREB-C\/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair","volume":"106","author":"D Ruffell","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI116663","article-title":"Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery","volume":"92","author":"S Ishibashi","year":"1993","journal-title":"J Clin Invest"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1126\/science.287.5455.1049","article-title":"Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation","volume":"287","author":"E Hirsch","year":"2000","journal-title":"Science"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1093\/brain\/awp240","article-title":"Off-target effects of epidermal growth factor receptor antagonists mediate retinal ganglion cell disinhibited axon growth","volume":"132","author":"MR Douglas","year":"2009","journal-title":"Brain"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1182\/blood.V95.8.2552","article-title":"Granulocyte-macrophage colony-stimulating factor stimulation results in phosphorylation of cAMP response element-binding protein through activation of pp90RSK","volume":"95","author":"EM Kwon","year":"2000","journal-title":"Blood"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1161\/CIRCULATIONAHA.106.633263","article-title":"Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule","volume":"114","author":"I Gotsman","year":"2006","journal-title":"Circulation"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/01.ATV.0000259365.31469.89","article-title":"Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis","volume":"27","author":"A Mor","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1084\/jem.20070366","article-title":"Phosphoinositide 3-kinase gamma participates in T cell receptor-induced T cell activation","volume":"204","author":"I Alcazar","year":"2007","journal-title":"J Exp Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1189\/jlb.0809585","article-title":"The catalytic PI3K isoforms p110gamma and p110delta contribute to B cell development and maintenance, transformation, and proliferation","volume":"87","author":"S Beer-Hammer","year":"2010","journal-title":"J Leukoc Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/1541-7786.MCR-10-0200","article-title":"A sensitized RNA interference screen identifies a novel role for the PI3K p110gamma isoform in medulloblastoma cell proliferation and chemoresistance","volume":"9","author":"AS Guerreiro","year":"2011","journal-title":"Mol Cancer Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"947858","DOI":"10.1155\/2011\/947858","article-title":"PI3K functions in cancer progression, anticancer immunity and immune evasion by tumors","volume":"2011","author":"F Dituri","year":"2011","journal-title":"Clin Dev Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1128\/MCB.12.5.2351","article-title":"Macrophage growth arrest by cyclic AMP defines a distinct checkpoint in the mid-G1 stage of the cell cycle and overrides constitutive c-myc expression","volume":"12","author":"CO Rock","year":"1992","journal-title":"Mol Cell Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0092-8674(94)90257-7","article-title":"Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation","volume":"79","author":"JY Kato","year":"1994","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1161\/01.ATV.0000184783.04864.9f","article-title":"Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency","volume":"25","author":"I Tabas","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"S Gordon","year":"2003","journal-title":"Nat Rev Immunol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0072674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:11:26Z","timestamp":1688433086000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0072674"}},"subtitle":[],"editor":[{"given":"Esther","family":"Lutgens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,8,22]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0072674","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,22]]}}}