Yang Xiao Ping, Yan Daoguang, Qiao Chunping, Liu Rui Jie, Chen Jer-Gin, Li Juan, Schneider Martina, Lagrost Laurent, Xiao Xiao, Jiang Xian-Cheng
Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1601-7. doi: 10.1161/01.ATV.0000085841.55248.13. Epub 2003 Jul 10.
Plasma phospholipid transfer protein (PLTP) is involved in the metabolism of HDL and apolipoprotein B (apoB)-containing lipoproteins. Atherosclerosis susceptibility is decreased in mice with PLTP deficiency that is associated with decreased liver production of apoB-containing lipoproteins and increase in their antioxidant. To investigate additionally the effect of PLTP on the development of atherosclerosis, we overexpressed PLTP in mice.
PLTP was overexpressed in apoE knockout mice using an adenovirus-associated virus (AAV)-mediated system. Plasma PLTP activity was 1.3- to 2-fold higher in mice injected with AAV-PLTP than in mice injected with control AAV-GFP, and PLTP levels were sustained during the experiment period (4 months). We show that 2-fold increased PLTP activity results in (1) a decrease in HDL cholesterol, HDL phospholipid, and apoAI levels; (2) a decrease in vitamin E contents in total plasma and in individual lipoprotein fractions; (3) an increase in lipoprotein oxidizability as assessed by copper-induced formation of conjugated dienes; (4) an increase in autoantibodies against oxidized apoB-containing particles; and (5) an increase in atherosclerosis lesions in proximal aorta.
These observations indicate that elevated plasma PLTP levels constitute a novel, long-term risk factor for atherosclerosis.
血浆磷脂转运蛋白（PLTP）参与高密度脂蛋白（HDL）和含载脂蛋白B（apoB）脂蛋白的代谢。PLTP缺乏的小鼠动脉粥样硬化易感性降低，这与肝脏含apoB脂蛋白生成减少及抗氧化能力增强有关。为进一步研究PLTP对动脉粥样硬化发展的影响，我们在小鼠中过表达了PLTP。
使用腺相关病毒（AAV）介导的系统在载脂蛋白E基因敲除小鼠中过表达PLTP。注射AAV-PLTP的小鼠血浆PLTP活性比注射对照AAV-GFP的小鼠高1.3至2倍，且在实验期间（4个月）PLTP水平持续升高。我们发现PLTP活性增加2倍会导致：（1）HDL胆固醇、HDL磷脂和载脂蛋白AI水平降低；（2）总血浆及各个脂蛋白组分中维生素E含量降低；（3）通过铜诱导共轭二烯形成评估的脂蛋白氧化能力增加；（4）针对氧化的含apoB颗粒的自身抗体增加；（5）近端主动脉粥样硬化病变增加。
这些观察结果表明，血浆PLTP水平升高是动脉粥样硬化的一个新的长期危险因素。
