Wolfe M S, Parks J S, Morgan T M, Rudel L L
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
Arterioscler Thromb. 1991 May-Jun;11(3):617-28. doi: 10.1161/01.atv.11.3.617.
African green monkeys were raised from birth to 60 months of age on diets containing cholesterol (0.8 mg/kcal) and enriched in polyunsaturated (polyunsaturated to saturated fat ratio [P:S] = 2.5) or saturated (P:S = 0.3) fat. Lipoproteins were isolated from plasma of a group of animals (N = 123) and were separated by gel filtration chromatography at 9, 14, 26, 38, and 50 months of age, which covered a period through adolescence into young adulthood. Total plasma cholesterol (TPC) concentrations were 16% lower (p = 0.01) in the polyunsaturated fat-fed group, and high density lipoprotein (HDL) cholesterol concentrations averaged 20% lower (p = 0.008) in this group between 14 and 50 months of age, while plasma apolipoprotein A-I (apo A-I) averaged 7% lower (p = 0.06) over this age interval in the animals. The HDL cholesterol to apo A-I ratio was found to be significantly lower (p = 0.006) in the animals fed the polyunsaturated fat diet. This suggested that the HDL subfraction distribution might differ between groups. In a subset of animals (n = 105, 64 male and 41 female), HDL was subfractionated by density gradient ultracentrifugation into six subfractions, HDL-I to HDL-VI, from lowest to highest density. The saturated fat-fed animals had significantly higher cholesterol concentrations in HDL-I and significantly lower cholesterol concentrations in HDL-III, HDL-IV, and HDL-V. These effects held across all ages studied; therefore, these diet effects were not age dependent. In both diet groups, the HDL subfraction pattern changed with age such that the HDL-I and HDL-II cholesterol concentrations decreased, and those of HDL-IV, HDL-V, and HDL-VI increased as the animals matured. The decrease in HDL-I with age appeared to result primarily from a decrease in HDL-I in males, while the HDL-I cholesterol concentration in females did not change with age. We conclude that diet, age, and gender all affect HDL subfraction distribution and therefore can potentially modify the relative atherogenicity of the plasma HDL populations. It remains for future studies to demonstrate the effectiveness of each subfraction in promoting or preventing the cholesterol deposition of atherosclerosis.
将出生后的非洲绿猴饲养至60个月龄,所喂饮食含有胆固醇(0.8毫克/千卡),并富含多不饱和脂肪(多不饱和脂肪与饱和脂肪的比例[P:S]=2.5)或饱和脂肪(P:S=0.3)。从一组动物(N=123)的血浆中分离出脂蛋白,并在9、14、26、38和50月龄时通过凝胶过滤色谱法进行分离,该时间段涵盖了从青春期到青年期。多不饱和脂肪喂养组的总血浆胆固醇(TPC)浓度低16%(p=0.01),在14至50月龄期间,该组的高密度脂蛋白(HDL)胆固醇浓度平均低20%(p=0.008),而在此年龄区间,动物血浆载脂蛋白A-I(apo A-I)平均低7%(p=0.06)。发现多不饱和脂肪饮食喂养的动物中HDL胆固醇与apo A-I的比值显著更低(p=0.006)。这表明两组之间HDL亚组分分布可能存在差异。在一部分动物(n=105,64只雄性和41只雌性)中,通过密度梯度超速离心将HDL亚分为六个亚组分,从最低密度到最高密度依次为HDL-I至HDL-VI。饱和脂肪喂养的动物中,HDL-I中的胆固醇浓度显著更高,而HDL-III、HDL-IV和HDL-V中的胆固醇浓度显著更低。这些效应在所有研究年龄中均存在;因此,这些饮食效应与年龄无关。在两个饮食组中,HDL亚组分模式均随年龄变化,随着动物成熟,HDL-I和HDL-II胆固醇浓度降低,而HDL-IV、HDL-V和HDL-VI的胆固醇浓度升高。HDL-I随年龄的降低似乎主要是由于雄性HDL-I的减少,而雌性HDL-I胆固醇浓度不随年龄变化。我们得出结论,饮食、年龄和性别均会影响HDL亚组分分布,因此可能会潜在改变血浆HDL群体的相对动脉粥样硬化性。未来的研究仍需证明每个亚组分在促进或预防动脉粥样硬化胆固醇沉积方面的有效性。