Björkegren J, Karpe F, Milne R W, Hamsten A
King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
J Lipid Res. 1998 Jul;39(7):1412-20.
Triglyceride-rich lipoproteins (TRLs) that are modified during alimentary lipemia and their remnants are indicated to play an important role in the development of atherosclerosis. Although recent studies in transgenic and gene knock-out animal models have shed new light on the function of different apolipoproteins (apos) in the metabolism of TRLs and on their respective role in atherogenesis in these models, little is known about the compositional properties of human chylomicron remnants and very low density lipoprotein (VLDL). To address this issue, apos E, C-I, C-II, and C-III and lipids (triglycerides, phospholipids and cholesterol) were measured in Svedberg flotation rate (Sf) 60-400 and Sf 20-60 subfractions of VLDL and chylomicron remnants isolated from fasting and postprandial plasma samples in ten normotriglyceridemic men. VLDL was separated from chylomicron remnants by immunoaffinity chromatography using monoclonal antibodies (4G3 and 5E11) recognizing apoB-100 but not apoB-48 epitopes. The triglyceride, cholesterol and apoC-II contents of large (Sf 60-400) chylomicron remnants were significantly higher compared with large VLDL particles, while the small (Sf 20-60) chylomicron remnants contained significantly more apoC-II molecules but fewer apoC-I molecules than small VLDL. Whereas the apoC-III contents of large chylomicrons decreased, the apoC-III contents of large VLDL increased postprandially. The cholesterol to triglyceride ratio of large VLDL particles increased transiently by 50% in response to the oral fat load, whereas the cholesterol to triglyceride ratio of large chylomicron remnant particles and small TRL remnants increased 50-100% throughout the entire postprandial period. The specific alterations of the apolipoprotein and lipid composition of chylomicron remnants and VLDL particles observed during alimentary lipemia are likely to target these lipoprotein species differently to metabolic routes and to confer both endogenous and exogenous remnant lipoprotein roles in atherogenesis.
富含甘油三酯的脂蛋白（TRL）在饮食性血脂异常期间发生修饰，其残粒被认为在动脉粥样硬化的发展中起重要作用。尽管最近在转基因和基因敲除动物模型中的研究为不同载脂蛋白（apo）在TRL代谢中的功能及其在这些模型中动脉粥样硬化发生中的各自作用提供了新的线索，但对于人类乳糜微粒残粒和极低密度脂蛋白（VLDL）的组成特性知之甚少。为了解决这个问题，在10名正常甘油三酯血症男性的空腹和餐后血浆样本中分离出的VLDL和乳糜微粒残粒的斯维德伯格漂浮率（Sf）60 - 400和Sf 20 - 60亚组分中，测量了apo E、C-I、C-II和C-III以及脂质（甘油三酯、磷脂和胆固醇）。使用识别apoB-100但不识别apoB-48表位的单克隆抗体（4G3和5E11）通过免疫亲和色谱法将VLDL与乳糜微粒残粒分离。与大的VLDL颗粒相比，大的（Sf 60 - 400）乳糜微粒残粒的甘油三酯、胆固醇和apoC-II含量显著更高，而小的（Sf 20 - 60）乳糜微粒残粒比小的VLDL含有显著更多的apoC-II分子但更少的apoC-I分子。大乳糜微粒的apoC-III含量下降，而大VLDL的apoC-III含量在餐后增加。大的VLDL颗粒的胆固醇与甘油三酯比值因口服脂肪负荷而短暂增加50%，而大的乳糜微粒残粒颗粒和小的TRL残粒的胆固醇与甘油三酯比值在整个餐后期间增加50 - 100%。在饮食性血脂异常期间观察到的乳糜微粒残粒和VLDL颗粒的载脂蛋白和脂质组成的特定改变可能使这些脂蛋白种类在代谢途径上受到不同的靶向作用，并赋予内源性和外源性残粒脂蛋白在动脉粥样硬化发生中的作用。
