Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice

摘要: Objective: Determination of the in vivo significance LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development absence its main ligand apoE. Methods Results: LRP1 knock-in mice carrying an inactivating mutation NPxYxxL motif were crossed with apoEdeficient mice. In apoE, relative to wild-type animals, mutated showed increased clearance postprandial lipids despite a compromised endocytosis rate inefficient insulin-mediated translocation receptor plasma membrane, likely due slow recycling receptor. Postprandial lipoprotein improvement was explained by hepatic triglyceride-rich remnant lipoproteins accompanied compensatory 1.6-fold upregulation LDLR expression hepatocytes. One year-old apoE-deficient having dysfunctional revealed 3-fold decrease spontaneous 2-fold reduction LDL-cholesterol levels. Conclusion: These findings demonstrate that is important for perinuclear endosomal recycling. impairments correlated reduced atherogenesis cholesterol levels mice, via upregulation.