APOLIPOPROTEIN E DEFICIENCY AND ATHEROSCLEROSIS

在人类中，载脂蛋白E（apoE）缺乏导致高脂血症 和血管疾病。 我们最近确定那个港口 海豹和海狮的血浆apoE水平不可检测， 但他们不会出现高脂血症或残余脂蛋白 通常见于apoE缺乏的人。海豹和海洋的饮食 狮子富含omega-3脂肪酸，可以抑制VLDL 合成，从而“掩盖”apoE缺乏的影响。 的 本研究的目的是：（1）确定 斑海豹和海狮的apoE缺乏，2）确定 海豹高效代谢富含维生素E的机制 脂蛋白，和3）以确定饮食中的ω-3脂肪酸的作用， 维持血脂正常 首先，我们将确定哪些载脂蛋白（S）负责 受体介导的海豹脂蛋白摄取， 培养技术和体内周转研究。 第二、 将进行实验，以确定是否港海豹和 海狮有apoE基因和apoE mRNA， 北方印迹技术。 分别 第三，我们将评估 通过喂养海豹来替代鱼类饮食的作用 高胆固醇和饱和脂肪等热量饮食。 这些脂蛋白代谢的研究在那个港口是独一无二的 海豹和海狮是动物模型， 可以研究apoE缺乏症。 因为它们的饮食结构 它们提供了一个独特的机会来确定 这种饮食的最大效果，特别是在面对apoE时 缺陷 因此，这些研究与以下目标高度相关： 了解饮食与脂蛋白代谢的关系 动脉粥样硬化的病因。

In humans, apolipoprotein E (apoE) deficiency causes hyperlipidemia and vascular disease. We have recently determined that harbor seals and sea lions do not have detectable levels of plasma apoE, yet they do not develop hyperlipidemia or remnant lipoproteins typically seen in apoE deficient humans. The diet of seals and sea lions is rich in omega-3 fatty acids and may suppress VLDL synthesis, thus "masking" the impact of the apoE deficiency. The objectives of this study are 1) to determine the basis for the apoE deficiency in harbor seals and sea lions, 2) to determine the mechanism by which seals efficiently metabolize triglyceride-rich lipoproteins, and 3) to determine the role of dietary omega-3 fatty in maintaining normolipemia. First, we will determine which apoprotein(s) are responsible for receptor-mediated uptake of seal lipoproteins using both cell culture techniques and in vivo turnover studies. Second, experiments will be conducted to determine whether harbor seals and sea lions have the apoE gene and apoE mRNA using Southern and Northern blotting techniques. respectively. Third, we will assess the role of the fish-diet by feeding seals an alternative isocaloric diet high in cholesterol and saturated fat. These studies of lipoprotein metabolism are unique in that harbor seals and sea lions are animal models in which the full impact of apoE deficiency can be studied. Because their diets are composed entirely of fish, they offer a unique opportunity to determine the maximal effect of such a diet, especially in the face of apoE deficiency. Thus these studies are highly relevant to the goal of understanding the relationship of diet and lipoprotein metabolism to the causation of atherosclerosis in man.