Nijstad Niels, de Boer Jan Freark, Lagor William R, Toelle Markus, Usher David, Annema Wijtske, der Giet Markus van, Rader Daniel J, Tietge Uwe J F
Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Biochim Biophys Acta. 2011 Apr;1811(4):294-9. doi: 10.1016/j.bbalip.2011.01.008. Epub 2011 Feb 3.
Apolipoprotein (apo) O is a newly discovered apolipoprotein preferentially contained within HDL; however, currently, no data are available on the (patho)physiological effects of apoO. Therefore, the present study assessed the impact of apoO overexpression on (i) plasma lipids and lipoproteins as well as on (ii) HDL functionality. Human apoO was overexpressed by means of recombinant adenovirus (AdhapoO) in human apoA-I transgenic mice, a humanized mouse model of HDL metabolism. AdhapoO substantially increased apoO in plasma and within HDL. However, plasma triglycerides, phospholipids, total cholesterol and HDL cholesterol did not change. HDL size distribution, lipid composition and the apoA-I and the apoO distribution over the different HDL fractions separated by FPLC remained unaltered. Furthermore, enrichment of HDL with apoO did not impact on HDL functionality assessed in four independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells, (ii) protection against LDL oxidation, (iii) anti-inflammatory activity on endothelial cells, and (iv) induction of vasodilation in isolated aortic rings ex vivo as a measure of stimulating vascular NO production. These results demonstrate that although overexpression of apoO results in a substantial enrichment of HDL particles with this novel apolipoprotein, apoO does not impact the plasma lipoprotein profile or HDL functionality.
载脂蛋白（apo）O是一种新发现的主要存在于高密度脂蛋白（HDL）中的载脂蛋白；然而，目前尚无关于apoO的（病理）生理作用的数据。因此，本研究评估了apoO过表达对（i）血浆脂质和脂蛋白以及（ii）HDL功能的影响。通过重组腺病毒（AdhapoO）在人apoA-I转基因小鼠（一种HDL代谢的人源化小鼠模型）中过表达人apoO。AdhapoO显著增加了血浆和HDL中的apoO。然而，血浆甘油三酯、磷脂、总胆固醇和HDL胆固醇并未改变。通过快速蛋白质液相色谱（FPLC）分离的不同HDL组分上的HDL大小分布、脂质组成以及apoA-I和apoO分布保持不变。此外，用apoO富集HDL并不影响以四种独立方式评估的HDL功能，即（i）刺激巨噬细胞泡沫细胞的胆固醇流出、（ii）防止低密度脂蛋白（LDL）氧化、（iii）对内皮细胞的抗炎活性以及（iv）离体分离主动脉环中的血管舒张诱导作为刺激血管一氧化氮（NO）产生的指标。这些结果表明，尽管apoO的过表达导致HDL颗粒大量富集这种新型载脂蛋白，但apoO并不影响血浆脂蛋白谱或HDL功能。
