ArticlePloS one2012
Apolipoprotein E4 is deficient in inducing macrophage ABCA1 expression and stimulating the Sp1 signaling pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet.Journal of proteome research · 2019Trial
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Genes Differentially Expressed Across Major Arteries Are Enriched in Endothelial Dysfunction-Related Gene Sets: Implications for Relative Inter-artery Atherosclerosis Risk.Bioinformatics and biology insights · 2024Article
- Apolipoprotein E and viral infection: Risks and Mechanisms.Molecular therapy. Nucleic acids · 2023Review
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases.International journal of molecular sciences · 2022Review
- Glycosylation of HDL-Associated Proteins and Its Implications in Cardiovascular Disease Diagnosis, Metabolism and Function.Frontiers in cardiovascular medicine · 2022Review
- Immunity and amyloid beta, total tau and neurofilament light chain: Findings from a community-based cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway.Frontiers in immunology · 2020Article
- ABCA1- and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease.Journal of lipid research · 2019Article
- Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight.Nature reviews. Immunology · 2018Review
- Article
- Akt isoform-dependent regulation of ATP-Binding cassette A1 expression by apolipoprotein E.Biochemical and biophysical research communications · 2016Article
- Differential Effects of apoE4 and Activation of ABCA1 on Brain and Plasma Lipoproteins.PloS one · 2016Article
- High-density lipoprotein-mediated transcellular cholesterol transport in mouse aortic endothelial cells.Biochemical and biophysical research communications · 2015Article
- Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2015Review
- A Subregion of Reelin Suppresses Lipoprotein-Induced Cholesterol Accumulation in Macrophages.PloS one · 2015Article
- APOε4 is associated with enhanced in vivo innate immune responses in human subjects.The Journal of allergy and clinical immunology · 2014Article
- Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature.BMC geriatrics · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
ATP binding cassette A1 (ABCA1) is a membrane protein that promotes cellular cholesterol efflux. Using RAW 264.7 macrophages, we studied the relative effects of apolipoprotein (apo) E3 and apoE4 on ABCA1 and on the signaling pathway that regulates its expression. Both lipid-associated and lipid-free apoE4 forms induced ~30% lower levels of ABCA1 protein and mRNA than apoE3 forms. Phosphorylated levels of phosphoinositol 3-kinase (PI3K), protein kinase Cζ (PKCζ) and specificity protein 1 (Sp1) were also lower when treated with apoE4 compared to apoE3. The reduced ability of apoE4 to induce ABCA1 expression, PKCζ and Sp1 phosphorylation were confirmed in human THP-1 monocytes/macrophages. Sequential phosphorylation of PI3K, PKCζ and Sp1 has been suggested as a mechanism for upregulation of ABCA1 expression. Both apoE3 and apoE4 reduced total cholesterol and cholesterol esters in lipid-laden RAW 264.7 cells, and induced apoAI-mediated cholesterol efflux. However, the cholesterol esters and cholesterol efflux in apoE4-treated cells were ~50% and ~24% lower, respectively, compared to apoE3-treated cells. Accumulation of cholesterol esters in macrophages is a mechanism for foam cell formation. Thus the reduced ability of apoE4 to activate the PI3K-PKCζ-Sp1 signaling pathway and induce ABCA1 expression likely impairs cholesterol ester removal, and increases foam cell formation.
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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.