Project 1- Mechanisms of Atherosclerosis Prevention

该项目旨在确定亚麻籽油的抗动脉粥样硬化作用。一种小鼠模型 动脉粥样硬化，B100+/+LDLR-/-小鼠，将进行研究，以利用与 人体中的脂蛋白组成。这项提议是直接比较饮食中的亚麻籽油 将2%的能量作为α-亚麻酸提供给含有足够鱼油的可比日粮 提供EPA+DHA作为能量的2%。这两种饮食都会被比作含有 饱和脂肪。建议进行更多的研究，以找到证明动脉粥样硬化保护所需的亚麻籽油的最低有效水平。所有饮食将包含10%的能量作为脂肪，不会在饮食中添加明显数量的胆固醇。我们将检查与饮食相关的血脂和脂蛋白代谢的差异，并将研究再循环灌流过程中肝脏脂肪积累和分泌的饮食反应。我们将在饮食暴露20周后量化动脉粥样硬化的质量和程度。根据初步数据，我们假设亚麻籽油对动脉粥样硬化的发展具有保护作用，尽管对血脂浓度的影响很小，但对肝脏的脂成分有显著的影响。我们预计，亚麻籽油和鱼油在血浆脂蛋白组成方面的相关差异将被识别为可能预测动脉粥样硬化减轻的差异。此外，我们将研究巨噬细胞对亚麻油和鱼油饮食的炎症反应，以及亚麻油中的ALA和鱼油中的EPA+DHA可以限制动脉粥样硬化的详细机制。

This project is designed to identify atheroprotective effects of flaxseed oil. A mouse model of atherosclerosis, the B100+/+LDLr-/- mouse, will be studied to take advantage of similarities to humans in lipoprotein composition. The proposal is to directly compare flaxseed oil in diets providing 2% of energy as alpha-linolenic acid to a comparable diet containing enough fish oil to provide EPA+DHA as 2% of energy. Both of these diets will be compared to a diet containing saturated fat. Additional studies are proposed to find minimal effective levels of flaxseed oil required to demonstrate atheroprotection. All diets will contain 10% of energy as fat with no appreciable amounts of cholesterol added to the diets. We will examine diet-related differences in plasma lipid and lipoprotein metabolism, and we will study the diet response of liver lipid accumulation and secretion during recirculating perfusion. We will quantify the quality and extent of aortic atherosclerosis after 20 weeks of diet exposure. Based on preliminary data, we hypothesize that flaxseed oil will provide protection against development of atherosclerosis in spite of minimal effects on plasma lipid concentrations but significant effects on liver lipid compositions. We anticipate that flaxseed oil and fish oil-related differences in plasma lipoprotein composition will be identified that may predict decreased atherosclerosis. Further, we will examine macrophage inflammatory responses to the flaxseed oil and fish oil diets and detail mechanisms through which the ALA from flaxseed oil and EPA+DHA from fish oil could limit atherosclerosis.