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As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGF\u03b2 and PDGFR\u03b2 in reverse cholesterol transport and the maintenance of vascular wall integrity. Here we used a knockin mouse model to uncover a novel atheroprotective role for LRP1 in macrophages where tyrosine phosphorylation of an NPxY motif in its intracellular domain initiates a signaling cascade along an LRP1\/SHC1\/PI3K\/AKT\/PPAR\u03b3\/LXR axis to regulate and integrate cellular cholesterol homeostasis through the expression of the major cholesterol exporter ABCA1 with apoptotic cell removal and inflammatory responses.<\/jats:p>","DOI":"10.7554\/elife.29292","type":"journal-article","created":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T11:17:39Z","timestamp":1510917459000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.29292","source":"Crossref","is-referenced-by-count":95,"title":["LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in 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