ArticleThe Journal of biological chemistry2007
Apolipoprotein E4 in macrophages enhances atherogenesis in a low density lipoprotein receptor-dependent manner.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Aortic Single-Cell Transcriptome Analysis Reveals ApoE-Isoform-Specific Influences on Vascular Disease.International journal of molecular sciences · 2026Article
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.Neurobiology of disease · 2025Article
- Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.Journal of atherosclerosis and thrombosis · 2025Review
- Correlations between the NMR Lipoprotein Profile,International journal of molecular sciences · 2023Article
- Multi-omics studies reveal ameliorating effects of physical exercise on neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- Genetics of Triglyceride-Rich Lipoproteins Guide Identification of Pharmacotherapy for Cardiovascular Risk Reduction.Cardiovascular drugs and therapy · 2021Review
- The Links between Cardiovascular Diseases and Alzheimer's Disease.Current neuropharmacology · 2021Review
- Beyond the CNS: The many peripheral roles of APOE.Neurobiology of disease · 2020Review
- Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol andWorld journal of gastroenterology · 2019Article
- New evidence from plasma ceramides links apoE polymorphism to greater risk of coronary artery disease in Finnish adults.Journal of lipid research · 2019Article
- Apoprotein E and Reverse Cholesterol Transport.International journal of molecular sciences · 2018Review
- APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study.Experimental gerontology · 2017Article
- 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
- Apolipoprotein E4 impairs macrophage efferocytosis and potentiates apoptosis by accelerating endoplasmic reticulum stress.The Journal of biological chemistry · 2012Article
- Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Apolipoprotein E4 exaggerates diabetic dyslipidemia and atherosclerosis in mice lacking the LDL receptor.Diabetes · 2011Article
- Homocysteine, another risk factor for Alzheimer disease, impairs apolipoprotein E3 function.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Apolipoprotein E (apoE) and the low density lipoprotein receptor (LDLr) are well recognized determinants of atherosclerosis. In addition to hepatocytes, where both are highly expressed and contribute to plasma lipoprotein clearance, they are expressed in vascular cells and macrophages. In this study, we examined the effects of human apoE isoforms and LDLr levels in atherogenic pathways in primary macrophages ex vivo and atherosclerosis development after bone marrow transfer in vivo using mice expressing human apoE isoforms and different levels of LDLr expression. Increases in LDLr expression significantly increased cholesterol delivery into macrophages in culture, and the effects were more prominent with lipoproteins containing apoE4 than those containing apoE3. Conversely, increased LDLr expression reduced cholesterol efflux in macrophages expressing apoE4 but not in macrophages expressing apoE3. Furthermore, apoE3 protected VLDL from oxidation in vitro more than did apoE4. In LDLr-deficient mice expressing the human apoE4 isoform, Apoe4/4 Ldlr-/-, the replacement of bone marrow cells with those expressing LDLr increased atherosclerotic lesions in a dose-dependent manner compared with mice transplanted with cells having no LDLr. In contrast, atherosclerosis in Apoe3/3 Ldlr-/- mice, expressing the human apoE3 isoform, did not differ by the levels of macrophage LDLr expression. Our results demonstrate that apoE4, but not apoE3, in macrophages enhances atherosclerotic plaque development in mice in an LDLr-dependent manner and suggests that this interaction may contribute to the association of apoE4 with an increased cardiovascular risk in humans.
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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.