Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells |
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Authors: | Sacre Sandra M Stannard Anita K Owen James S |
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Affiliation: | Department of Medicine, Royal Free and University College Medical School, University College London, Royal Free Campus, London NW3 2PF, UK. |
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Abstract: | 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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Keywords: | Apolipoprotein E receptor 2 EA.hy926 cells Nitric oxide synthase PI3-kinase Tyrosine phosphorylation |
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