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Although the activation of Wnt\/\u03b2\u2010catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low\u2010density lipoprotein (LDL) receptor\u2010related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild\u2010type (WT) and LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt\/\u03b2\u2010catenin gene expression while in the HC LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice Wnt\/\u03b2\u2010catenin pathway was shut down. Functionally, HC induced pro\u2010inflammatory gene expression in LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Furthermore, in WT mice PSE increased anti\u2010inflammatory genes expression and inhibited Wnt\/\u03b2\u2010catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5<jats:sup>\u2212\/\u2212<\/jats:sup> mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti\u2010inflammatory, pro\u2010survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.<\/jats:p>","DOI":"10.1038\/icb.2015.41","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T09:12:41Z","timestamp":1425892361000},"page":"653-661","source":"Crossref","is-referenced-by-count":25,"title":["LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes"],"prefix":"10.1111","volume":"93","author":[{"given":"Maria","family":"Borrell\u2010Pages","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, CSIC\u2010ICCC, Hospital de la Santa Creu i Sant Pau, IIB\u2010Sant Pau  Barcelona Spain"},{"name":"Cardiovascular Research Chair, UAB  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"July","family":"Carolina Romero","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, CSIC\u2010ICCC, Hospital 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