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.

中文翻译：

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LRP1 整合鼠巨噬细胞胆固醇稳态和动脉粥样硬化的炎症反应

低密度脂蛋白受体相关蛋白 1 (LRP1) 是一种多功能细胞表面受体，具有多种生理作用，从细胞内吞作用摄取脂蛋白和其他货物到细胞外环境的传感器和广泛信号机制的整合者。作为乳糜微粒残余受体，LRP1 与肝脏中的 LDL 受体一起控制全身脂质代谢，而在平滑肌细胞 (SMC) 中，LRP1 在胆固醇反向转运和维持血管壁中作为 TGFβ 和 PDGFRβ 的共同受体起作用正直。