Stevenson S C, Sawyer J K, Rudel L L
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C. 27103.
Arterioscler Thromb. 1992 Jan;12(1):28-40. doi: 10.1161/01.atv.12.1.28.
Significant differences among individuals occur in the lipoprotein response to atherogenic diets in cynomolgus and African green monkeys. The range of concentrations of total plasma cholesterol (TPC) was 100-600 mg/dl and of apolipoprotein (apo) E (quantified by enzyme-linked immunosorbent assay) was 3-20 mg/dl in the animal groups of this study. The correlation between the concentrations of TPC and of apo E was r = 0.89 in these animals. To determine which lipoprotein classes contained the majority of apo E, agarose gel-filtration chromatography was used to subfractionate whole plasma. In hypercholesterolemic monkeys, the majority of the apo E and apo B-100 coeluted within the region of low density lipoprotein (LDL). In normocholesterolemic monkeys, the majority of apo E coeluted with apo A-I and high density lipoproteins. A strong positive correlation was seen between the concentrations of plasma apo E and LDL cholesterol (r = 0.9), but there was no significant correlation between high density lipoprotein apo E and either TPC or plasma apo E concentrations. A positive correlation of r = 0.8 was found between the LDL apo E to apo B-100 molar ratio and the average LDL particle size, suggesting an increase in the number of apo E molecules on the larger LDL particles. Within individual animals, LDL were heterogeneous and the LDL subfractions of lower density (1.02 less than d less than 1.03 g/ml) had the highest proportion of apo E, although apo E was present on LDL of all densities. A strong positive correlation between plasma apo E concentration and coronary artery atherosclerosis was identified, and in stepwise regression analysis, plasma apo B concentration and the apo E to apo B molar ratio of LDL together accounted for more than 90% of the variation in the atherosclerosis end point of coronary artery intimal area. These data strongly suggest that the enrichment of LDL with cholesteryl esters and apo E, which occurs in hypercholesterolemic primates, is an atherogenic feature of the plasma lipoproteins.
食蟹猴和非洲绿猴对致动脉粥样化饮食的脂蛋白反应在个体间存在显著差异。在本研究的动物组中，总血浆胆固醇（TPC）浓度范围为100 - 600mg/dl，载脂蛋白（apo）E（通过酶联免疫吸附测定法定量）浓度范围为3 - 20mg/dl。在这些动物中，TPC浓度与apo E浓度的相关性为r = 0.89。为了确定哪些脂蛋白类别含有大部分的apo E，采用琼脂糖凝胶过滤色谱法对全血浆进行亚分级分离。在高胆固醇血症猴中，大部分的apo E和apo B - 100在低密度脂蛋白（LDL）区域内共洗脱。在正常胆固醇血症猴中，大部分的apo E与apo A - I和高密度脂蛋白共洗脱。血浆apo E浓度与LDL胆固醇浓度之间呈现出强正相关（r = 0.9），但高密度脂蛋白apo E与TPC或血浆apo E浓度之间无显著相关性。在LDL的apo E与apo B - 100摩尔比和平均LDL颗粒大小之间发现了r = 0.8的正相关，表明较大LDL颗粒上的apo E分子数量增加。在个体动物体内，LDL是异质性的，低密度（1.02＜d＜1.03g/ml）的LDL亚组分中apo E比例最高，尽管所有密度的LDL上都存在apo E。血浆apo E浓度与冠状动脉粥样硬化之间存在强正相关，并且在逐步回归分析中，血浆apo B浓度和LDL的apo E与apo B摩尔比共同占冠状动脉内膜面积动脉粥样硬化终点变异的90%以上。这些数据强烈表明，在高胆固醇血症灵长类动物中发生的LDL富含胆固醇酯和apo E是血浆脂蛋白的致动脉粥样化特征。
