Project 1- Mechanisms of Atherosclerosis Prevention

项目1-动脉粥样硬化预防机制

• 批准号: 6946076
• 负责人: Lawrence L Rudel
• 金额: $ 24.26万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946076
• 关键词: alternative medicine; angiosperms; atherosclerosis; cardiovascular disorder prevention; cholesterol; diet therapy; dietary lipid; dietary supplements; genetically modified animals; immune response; inflammation; laboratory mouse; lipid metabolism; macrophage; marine animal oil; nutrition related tag; plant extracts; saturated fat; unsaturated fatty acids; vegetable oils

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.

该项目旨在确定亚麻籽油的动脉粥样硬化保护作用。的小鼠模型 将研究B100+/+LDLr-/-小鼠动脉粥样硬化，以利用与 人的脂蛋白组成。建议是直接比较饮食中的亚麻籽油 提供2%的能量作为α-亚麻酸，以含有足够鱼油的可比饮食， EPA+DHA占能量的2%。这两种饮食都将与含有 饱和脂肪建议进行额外的研究，以找到证明动脉粥样硬化保护所需的最低有效水平的亚麻籽油。所有的饮食将包含10%的能量作为脂肪，没有明显数量的胆固醇添加到饮食中。我们将检查饮食相关的血浆脂质和脂蛋白代谢的差异，我们将研究再循环灌注过程中肝脏脂质积累和分泌的饮食反应。我们将在饮食暴露20周后量化主动脉粥样硬化的质量和程度。根据初步数据，我们假设亚麻籽油将提供保护，防止动脉粥样硬化的发展，尽管对血浆脂质浓度的影响很小，但对肝脏脂质成分的显着影响。我们预计亚麻籽油和鱼油相关的血浆脂蛋白组成的差异将被确定，可能预测减少动脉粥样硬化。此外，我们将研究巨噬细胞对亚麻籽油和鱼油饮食的炎症反应，并详细说明亚麻籽油中的ALA和鱼油中的EPA+DHA可以限制动脉粥样硬化的机制。