Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/75284
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dc.contributor.authorRecio Cruz, Carlota Pilaren_US
dc.contributor.authorOguiza, Ainhoaen_US
dc.contributor.authorLazaro, Iolandaen_US
dc.contributor.authorMallavia, Beñaten_US
dc.contributor.authorEgido, Jesusen_US
dc.contributor.authorGomez-Guerrero, Carmenen_US
dc.date.accessioned2020-11-09T16:34:04Z-
dc.date.available2020-11-09T16:34:04Z-
dc.date.issued2014en_US
dc.identifier.issn1079-5642en_US
dc.identifier.urihttp://hdl.handle.net/10553/75284-
dc.description.abstractObjective— Activation of Janus kinase/signal transducers and activators of transcription (STAT) pathway by hyperglycemia and dislypidemia contributes to the progression of diabetic complications, including atherosclerosis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate Janus kinase/STAT and have emerged as promising target for anti-inflammatory therapies. We investigated whether a cell-permeable lipopeptide corresponding to the kinase inhibitory region of SOCS1 could reduce atherosclerosis in diabetic mice and identified the mechanisms involved. Approach and Results— Streptozotocin-induced diabetic apolipoprotein E–deficient mice (aged 8 and 22 weeks) were given intraperitoneal injections of vehicle, SOCS1-derived peptide, or control mutant peptide for 6 to 10 weeks. SOCS1 therapy suppressed STAT1/STAT3 activation in atherosclerotic plaques of diabetic mice and significantly reduced lesion size at both early and advanced stages of lesion development compared with vehicle group. Plaque characterization demonstrated that SOCS1 peptide decreased the accumulation of lipids, macrophages, and T lymphocytes, whereas increasing collagen and smooth muscle cell content. This atheroprotective effect was accompanied by systemic (reduced proinflammatory Ly6Chigh monocytes and splenic cytokine expression) and local (reduced aortic expression of chemokines and cytokines) mechanisms, without impact on metabolic parameters. In vitro, SOCS1 peptide dose dependently inhibited STAT1/STAT3 activation and target gene expression in vascular smooth muscle cells and macrophages and also suppressed cytokine-induced cell migration and adhesion processes. Conclusions— SOCS1-based targeting Janus kinase/STAT restrains key mechanisms of atherogenesis in diabetic mice, thereby preventing plaque formation and increasing plaque stability. Approaches to mimic native SOCS1 functions may have a therapeutic potential to retard the progression of diabetic complications.en_US
dc.languageengen_US
dc.relationSAF2009-11794en_US
dc.relationSAF2012-38830en_US
dc.relationFIS PI10/00072en_US
dc.relation.ispartofArteriosclerosis, Thrombosis, and Vascular Biologyen_US
dc.sourceArteriosclerosis, Thrombosis, and Vascular Biology [ISSN 1079-5642], v. 34 (9), p. 1953–1960en_US
dc.subject320502 Endocrinologíaen_US
dc.titleSuppressor of Cytokine Signaling 1–Derived Peptide Inhibits Janus Kinase/Signal Transducers and Activators of Transcription Pathway and Improves Inflammation and Atherosclerosis in Diabetic Miceen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1161/ATVBAHA.114.304144en_US
dc.description.lastpage1960en_US
dc.identifier.issue9-
dc.description.firstpage1953en_US
dc.relation.volume34en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.utils.revisionen_US
dc.identifier.ulpgcNoen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.sjr3,503
dc.description.jcr6,008
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
item.grantfulltextopen-
item.fulltextCon texto completo-
crisitem.author.orcid0000-0002-8832-2826-
crisitem.author.fullNameRecio Cruz, Carlota Pilar-
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