DIETARY CHOLESTEROL AS HIGH DENSITY LIPOPROTEIN METABOLISM REGULATOR IN RABBITS

新西兰白色兔出现高胆固醇血症， 高脂蛋白血症和动脉粥样硬化 含有1%（w/w）胆固醇的组合物中，持续4 - 8周。 主导 这种胆固醇诱导的高脂蛋白血症的特征是 β-极低密度脂蛋白（β-VLDL）的出现， 一种致动脉粥样硬化血浆脂蛋白颗粒，其富含 载脂蛋白E（apoE）和胆固醇酯（CE）。 还有 高密度脂蛋白（HDL）水平急剧下降， 胆固醇喂养的兔子的血浆。 HDL颗粒是抗- 富含载脂蛋白A-1（apoA-1）和CE。 这项研究计划的目的是提供一种生物化学方法， 对胆固醇中HDL颗粒消失的解释 喂兔子 它们的消失可能是由于 合成或增加催化剂或两者。 HDL2和 HDL组分的HDL 3亚组分将通过 聚丙烯酰胺凝胶电泳和聚阴离子沉淀法 技术. 凝胶将用密度计扫描，并且 正常和胆固醇血症家兔的HDL 2和HDL 3峰面积 将被比较。 此外，胆固醇和载脂蛋白A-1含量 这两个HDL亚类的浓度将用酶法测定。 检测将确定这两个HDL亚类中的哪一个正在下降 在高胆固醇喂养的兔子身上。 他们还将确定apoA- 1和胆固醇正在从其中一个或两个中消失 粒子以相等的速率运动。 由于载脂蛋白A-1和胆固醇是 从这些粒子中的一个或两个以相等的速率消失。 由于apoA-1是HDL组分中的主要载脂蛋白， 饮食中胆固醇的调节将被用来作为一个模型， 饮食中的胆固醇正在从其中一种或两种中消失 粒子以相同的速度运动。 由于apoA-1是主要的载脂蛋白， 在HDL组分中，其通过膳食胆固醇的调节将是 用作膳食胆固醇如何调节 肝脏和小肠中HDL的合成。 单特异性 兔apoA-抗血清将用于定量 从标记肝细胞和标记的小细胞免疫沉淀apoA-1 肠粘膜细胞，以定位apoA的主要位点， 1合成正常和胆固醇血症兔以及 确定膳食胆固醇对apoA- 在这些器官中合成。 apoA-1的相对比率 合成将表示为总蛋白质的百分比 合成了 这项研究有望提供有用的 关于饮食调节的机制的生物化学信息 胆固醇调节HDL水平的降低， 动脉粥样硬化在兔子和可能在人。我们的长期 目的是确定生物学机制， 饮食胆固醇调节动脉粥样硬化的代谢， 抗动脉粥样硬化血浆脂蛋白。

New Zealand White rabbits develop hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis when fed a diet containing 1% (w/w) cholesterol for 4-8 weeks. A predominant characteristic of this cholesterol-induced hyperlipoproteinemia is the appearance of beta-very low density lipoprotein (beta-VLDL), an atherogenic plasma lipoprotein particle, which is rich in apoliprotein E (apoE) and cholesteryl esters (CE). There is also a dramatic reduction in high density lipoprotein (HDL) levels in the plasma of cholesterol-fed rabbits. HDL particles are anti- atherogenic and are rich in apolipoprotein A-1 (apoA-1) and CE. It is the aim of this research plan to provide a biochemical explanation for the disappearance of HDL particles in cholesterol- fed rabbits. Their disappearance may be due to a decrease in synthesis or to an increase in catabolism or to both. The HDL2 and HDL3 subfractions of the HDL fraction will be separated by polyacrylamide gel electrophoresis and by polyanion precipitation techniques. The gels will be scanned with a densitometer, and the HDL2 and HDL3 peak areas for normal and cholesterolemic rabbits will be compared. In addition, the cholesterol and apoA-1 content of these two HDL subclasses will be measured with an enzymatic assay will determine which of these two HDL subclasses is declining in the cholesterol-fed rabbit. They will also determine if apoA- 1 and cholesterol are disappearing from one or both of these particles at equal rates. Since apoA-1 and cholesterol are disappearing from one or both of these particles at equal rates. Since apoA-1 is the major apolipoprotein in the HDL fraction, its regulation by dietary cholesterol will be used as a model of how dietary cholesterol are disappearing from one or both of these particles at equal rates. Since apoA-1 is the major apolipoprotein in the HDL fraction, its regulation by dietary cholesterol will be used as a model of how dietary cholesterol regulates the rate of HDL synthesis in the liver and small intestine. A monospecific antisera for rabbit apoA-will be used to quantitatively immunoprecipate apoA-1 from labeled hepatocytes and labeled small intestine mucosal cells in order to locate the major site of apoA- 1 synthesis in normal and cholesterolemic rabbits as well as to determine the effect of dietary cholesterol on the rates of apoA- 1 synthesis in these organs. The relative rates of apoA-1 synthesis will be expressed as the percent of total protein synthesized. This research is expected to provide useful biochemical information about the mechanisms by which dietary cholesterol regulates the reduction in HDL levels and the induction of atherosclerosis in rabbits and possibly in man. Our long-term objectives are to determine the biological mechanisms by which dietary cholesterol regulates the metabolism of atherogenic and anti-atherogenic plasma lipoproteins.