Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells
Open accessAbstract
Although apolipoprotein E3 (apoE3) is atheroprotective, two common isoforms, apoE2 and apoE4, produce recessive and dominant hyperlipidaemias, respectively. Using a fluorescent assay, we report herein that apoE3 particles secreted from recombinant cells stimulate more nitric oxide release in cultured human EA.hy926 endothelial cells than apoE2 or apoE4 (141% more than controls vs. 61 or 11%). Phosphatidylinositol (PI) 3‐kinase inhibitors suppressed the apoE effect, while apoE receptor 2 (apoER2) was tyrosine phosphorylated. We conclude that apoE stimulates endothelial nitric oxide release in an isoform‐dependent manner, and propose that tyrosine phosphorylation of apoER2 initiates PI3‐kinase signalling and activation of nitric oxide synthase.
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Phosphorylation of the tyrosine residue of the NPxY motif could abolish the interaction between the receptor and SNX17.
“The interaction between the receptor and adaptor protein could be abolished by phosphorylation of the tyrosine residue of the NPxY motif [62], as has been reported for LRP1 [63].”
From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [62]
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The role of nitric oxide in cardiovascular diseases
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- Authors
- Sacre, S. M., Stannard, A. K., & Owen, J. S.
- Affiliations
- The Royal Free Hospital (GB)
- Corresponding author
- Owen, James S
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2003-03-18
- Volume
- 540
- Issue
- 1-3
- Pages
- 181-187
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2091622438
- Cited by
- 73
- References
- 6
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 10 · 2013: 3 · 2012: 3
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E isoforms, APOE2, APOE3, APOE ε4, nitric oxide production, endothelial cells, EA.hy926 cells, tyrosine phosphorylation, nitric oxide synthase, hyperlipidemia, atheroprotection
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Androstadienes, Animals, Apolipoproteins E, Cells, Cultured, Endothelium, Vascular, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Cricetinae, Humans, Nitric Oxide, Phosphorylation, Tyrosine, CHO Cells, Protein Isoforms
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