Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells.
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.
Sacre
Sandra M
SM
Department of Medicine, Royal Free and University College Medical School, University College London, Royal Free Campus, London NW3 2PF, UK.
Stannard
Anita K
AK
Owen
James S
JS
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D020033:Protein Isoforms / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D009569:Nitric Oxide; D014443:Tyrosine; D000077191:Wortmannin