@article{8e8a6bcc5c0b439fb03437842ff072b7,
title = "LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis",
abstract = "Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. 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 TGFβ and PDGFRβ 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/PPARγ/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.",
author = "Xunde Xian and Yinyuan Ding and Marco Dieckmann and Li Zhou and Florian Plattner and Mingxia Liu and Parks, {John S.} and Hammer, {Robert E} and Philippe Boucher and Shirling Tsai and Joachim Herz",
note = "Funding Information: This work was supported by NIH grant R37 HL063762, R01 NS093382 and RF1 AG053391 (to JH). JH is further supported by the Consortium for Frontotemporal Dementia Research and the Bright Focus Foundation. ST is supported by North Texas Veterans Affairs Health Care Systems and the American Surgical Association Foundation Award. PB is supported by grants from Fondation de France, Fondation pour la Recherche M{\'e}dicale (FRM), the Agence Nationale de la Recherche (ANR-06-Physio-032–01 and ANR-09-BLAN-0121–01). JSP is supported by grants from National Institute of Health R01 HL119983 and R01 HL119962. We are indebted to Hoang Dinh Huynh and Yihong Wan for assistance with the bone marrow transplant model; Rebekah Hewitt, Huichuan Reyna, Issac Rocha, Tamara Terrones, Sandy Turner, Grant Richards, John Shelton, Nancy Heard and Barbara Dacus for their excellent technical assistance. Publisher Copyright: {\textcopyright} Xian et al.",
year = "2017",
month = nov,
day = "16",
doi = "10.7554/eLife.29292",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}