APOLIPOPROTEIN E DEFICIENCY AND ATHEROSCLEROSIS

在人类中，载脂蛋白E(ApoE)缺乏会导致高脂血症 和血管疾病。我们最近确定了那个港口 海豹和海狮没有检测到的血浆载脂蛋白E水平， 然而，他们不会患上高脂血症或残余脂蛋白。 通常见于载脂蛋白E缺陷的人类。海豹和海洋的饮食 狮子富含omega-3脂肪酸，可能会抑制极低密度脂蛋白 合成，从而“掩盖”载脂蛋白E缺乏的影响。这个 这项研究的目标是：1)确定 海豹和海狮的载脂蛋白缺乏，2)确定 海豹高效代谢富含甘油三酯的机制 脂蛋白，以及3)确定饮食中omega-3脂肪的作用 维持正常的血脂水平。 首先，我们将确定哪些载脂蛋白(S)负责 受体介导的两种细胞摄取海豹脂蛋白 培养技术和体内周转研究。第二, 将进行实验，以确定港口海豹和 利用Southern和免疫印迹技术检测到海狮的apoE基因和apoE mRNA 北方印迹技术。分别进行了分析。第三，我们将评估 鱼饲料的作用--通过喂养海豹来替代 高胆固醇和饱和脂肪的等卡路里饮食。 这些对脂蛋白新陈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，在这些动物模型中， 载脂蛋白E缺乏症可以研究。因为它们的饮食是由 完全由鱼制成，它们提供了一个独特的机会来确定 这种饮食的最大效果，尤其是在面对载脂蛋白E时 缺乏症。因此，这些研究与以下目标高度相关 认识饮食与脂蛋白代谢的关系 人类动脉粥样硬化的原因。

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.