ArticleArteriosclerosis, thrombosis, and vascular biology2008
Human LDL receptor enhances sequestration of ApoE4 and VLDL remnants on the surface of hepatocytes but not their internalization in mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Hnf1aos1 as a Metabolic Coordinator of Hepatic Lipid Homeostasis and Feedback Control.Non-coding RNA · 2026Article
- Pig and Mouse Models of Hyperlipidemia and Atherosclerosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology.International journal of molecular sciences · 2021Article
- Differences in Recycling of Apolipoprotein E3 and E4-LDL Receptor Complexes-A Mechanistic Hypothesis.International journal of molecular sciences · 2021Article
- Review
- Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases.Frontiers in physiology · 2021Review
- APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals.Frontiers in nutrition · 2021Article
- Beyond the CNS: The many peripheral roles of APOE.Neurobiology of disease · 2020Review
- Review
- γ-Secretase Inhibition Lowers Plasma Triglyceride-Rich Lipoproteins by Stabilizing the LDL Receptor.Cell metabolism · 2018Article
- ApoE knockout and knockin mice: the history of their contribution to the understanding of atherogenesis.Journal of lipid research · 2016Article
- Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner.Neurobiology of disease · 2014Article
- Diabetic atherosclerosis in APOE*4 mice: synergy between lipoprotein metabolism and vascular inflammation.Journal of lipid research · 2013Article
- Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease.Human molecular genetics · 2012Article
- Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.Journal of lipid research · 2011Review
- Apolipoprotein E4 exaggerates diabetic dyslipidemia and atherosclerosis in mice lacking the LDL receptor.Diabetes · 2011Article
- Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoproteinE4.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Apolipoprotein E knock-out and knock-in mice: atherosclerosis, metabolic syndrome, and beyond.Journal of lipid research · 2009Article
- Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice.International journal of obesity (2005) · 2008Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveIn humans, apolipoprotein (apo) E4 is associated with elevated plasma cholesterol levels and a high risk of developing atherosclerosis, whereas apoE2 is protective. Here we investigate the mechanism by which mice expressing human apoE isoforms recapitulate this association when they also express high levels of human low-density lipoprotein receptor (LDLR). METHODS AND
resultsPrimary hepatocytes from apoE4 mice secreted less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression decreased this secretion and increased degradation of apoE4. An apoE4-GFP fusion protein expressed in the liver of apoE-deficient mice accumulated on the hepatocyte surface bordering the space of Disse in an LDLR-dependent manner. Fluorescence-labeled very low-density lipoprotein (VLDL) remnants accumulated on the hepatocyte surface in apoE4 mice with high LDLR, but they were internalized poorly. In contrast, apoE2-GFP did not accumulate on the hepatocyte surface even when the LDLR expression was high, but apoE2 mice with high LDLR internalized the remnants avidly without sequestering them on the hepatocyte surface.
conclusionsThe high affinity of apoE4 to the LDLR enhances VLDL sequestration on the hepatocyte surface but delays their internalization. This delay likely increases VLDL conversion to cholesterol-enriched remnants in apoE4 mice with high LDLR, and probably to LDL in humans with apoE4.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.