ArticleArteriosclerosis, thrombosis, and vascular biology2013
Molecular mechanisms responsible for the differential effects of apoE3 and apoE4 on plasma lipoprotein-cholesterol levels.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 72 citations in OpenAlex.
- APOE ɛ4 Is Associated with Postprandial Inflammation in Older Adults with Metabolic Syndrome Traits.Nutrients · 2021Trial
- Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial.Journal of Alzheimer's disease : JAD · 2020Trial
- Genetic insights into coronary heart disease in the Teochew population: Bridging gaps in precision medicine.World journal of cardiology · 2026Article
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Correlation ofWorld journal of cardiology · 2025Article
- ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.Scientific reports · 2025Article
- In silico metabolic modelling links microbiome-derived metabolites to risk factors of Alzheimer's disease.Gut microbes reports · 2025Article
- Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.International journal of obesity (2005) · 2024Review
- Human apolipoprotein E glycosylation and sialylation: from structure to function.Frontiers in molecular neuroscience · 2024Review
- Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies.Molecular neurodegeneration · 2022Review
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Using lipid profiling to better characterize metabolic differences in apolipoprotein E (APOE) genotype among community-dwelling older Black men.GeroScience · 2022Article
- Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations.International journal of environmental research and public health · 2022Review
- Pig and Mouse Models of Hyperlipidemia and Atherosclerosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Beyond the CNS: The many peripheral roles of APOE.Neurobiology of disease · 2020Review
- Review
- Influence of 6 genetic variants on the efficacy of statins in patients with dyslipidemia.Journal of clinical laboratory analysis · 2018Article
- In the Heart of the Amazon: Noncommunicable Diseases and Apolipoprotein E4 Genotype in the Riverine Population.International journal of environmental research and public health · 2018Article
- Atomistic Insights into Structural Differences between E3 and E4 Isoforms of Apolipoprotein E.Biophysical journal · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe goal of this study was to understand the molecular basis of how the amino acid substitution C112R that distinguishes human apolipoprotein (apo) E4 from apoE3 causes the more proatherogenic plasma lipoprotein-cholesterol distribution that is known to be associated with the expression of apoE4. APPROACH AND
resultsAdeno-associated viruses, serotype 8 (AAV8), were used to express different levels of human apoE3, apoE4, and several C-terminal truncation and internal deletion variants in C57BL/6 apoE-null mice, which exhibit marked dysbetalipoproteinemia. Plasma obtained from these mice 2 weeks after the AAV8 treatment was analyzed for cholesterol and triglyceride levels, as well as for the distribution of cholesterol between the lipoprotein fractions. Hepatic expression of apoE3 and apoE4 induced similar dose-dependent decreases in plasma cholesterol and triglyceride to the levels seen in control C57BL/6 mice. Importantly, at the same reduction in plasma total cholesterol, expression of apoE4 gave rise to higher very low-density lipoprotein-cholesterol (VLDL-C) and lower high-density lipoprotein-cholesterol levels relative to the apoE3 situation. The C-terminal domain and residues 261 to 272 in particular play a critical role, because deleting them markedly affected the performance of both isoforms.
conclusionsApoE4 possesses enhanced lipid and VLDL-binding ability relative to apoE3, which gives rise to impaired lipolytic processing of VLDL in apoE4-expressing mice. These effects reduce VLDL remnant clearance from the plasma compartment and decrease the amount of VLDL surface components available for incorporation into the high-density lipoprotein pool, accounting for the more proatherogenic lipoprotein profile (higher VLDL-C/high-density lipoprotein-cholesterol ratio) occurring in apoE4-expressing animals compared with their apoE3 counterparts.
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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.