Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia A New Model for Combined Hyperlipidemia
Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia A New Model for Combined Hyperlipidemia
复制标题
DOI：
10.1161/atvbaha.109.190264
复制
发表时间：
2009-12-01
影响因子：
8.7
通讯作者：
Fan, Jianglin
中科院分区：
文献类型：
--
作者：
Koike, Tomonari;Kitajima, Shuji;Fan, Jianglin
β-载脂蛋白AII（apoAII）是高密度脂蛋白（HDL）中的第二大载脂蛋白。然而，载脂蛋白AII在脂蛋白代谢的生理功能还没有完全阐明。方法和结果，我们产生的人载脂蛋白AII转基因（Tg）兔，一个物种，通常没有内源性载脂蛋白AII基因。Tg兔中人apoAII的血浆水平约为30 mg/dL，与健康人的血浆水平相似。人载脂蛋白AII在Tg兔的表达导致血浆甘油三酯，总胆固醇和磷脂的水平增加，伴随着显着降低HDL-胆固醇水平相比，非Tg同窝仔。脂蛋白组分的分析表明，Tg兔表现出的高脂血症是由极低密度脂蛋白（VLDL）和中密度脂蛋白水平升高引起的。此外，肝素后脂蛋白脂酶活性显着降低Tg兔相比，非Tg rabbes. Conclusions，这些结果表明，载脂蛋白AII起着重要的作用，在极低密度脂蛋白和高密度脂蛋白代谢，可能通过抑制脂蛋白脂酶活性。ApoA Ⅱ Tg兔可能成为研究人类家族性混合型高脂血症的新模型。（Arterioscler Thromb Vasc Biol.2009;29：2047-2053.）
Objective-Apolipoprotein AII (apoAII) is the second major apolipoprotein in high-density lipoprotein (HDL). However, the physiological functions of apoAII in lipoprotein metabolism have not been fully elucidated.Methods and Results-We generated human apoAII transgenic (Tg) rabbits, a species that normally does not have an endogenous apoAII gene. Plasma levels of human apoAII in Tg rabbits were approximate to 30 mg/dL, similar to the plasma levels in healthy humans. The expression of human apoAII in Tg rabbits resulted in increased levels of plasma triglycerides, total cholesterol, and phospholipids accompanied by a marked reduction in HDL-cholesterol levels compared with non-Tg littermates. Analysis of lipoprotein fractions showed that hyperlipidemia exhibited by Tg rabbits was caused by elevated levels of very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins. Furthermore, postheparin lipoprotein lipase activity significantly decreased in Tg rabbits compared with non-Tg rabbits.Conclusions-These results indicate that apoAII plays an important role in both VLDL and HDL metabolism, possibly through the inhibition of lipoprotein lipase activity. ApoAII Tg rabbits may become a new model for the study of human familial combined hyperlipidemia. (Arterioscler Thromb Vasc Biol. 2009;29:2047-2053.)