EFFECTS OF DIET AND GENOTYPE ON ATHEROSCLEROSIS

饮食和基因型对动脉粥样硬化的影响

• 批准号: 5225826
• 负责人: DAVID L RAINWATER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5225826
• 关键词: atherosclerosis; atherosclerotic plaque; blood lipoprotein; cholesterol; diet; dietary lipid; disease /disorder model; genetic strain; high density lipoproteins; hyperlipoproteinemia; low density lipoprotein; model design /development; nutrition related tag; opossums; phenotype; postmortem; saturated fat; unsaturated fats; very low density lipoprotein

The ultimate goal of this project is to establish the laboratory opossum, Monodelphis domestica, as a unique model for determining the effects of diet and genotype on lipoprotein phenotypes and development of atherosclerosis. In conjunction with Project 5 and 6 Project 4 will help identify specific genes that control dietary responsiveness and ascertain their mechanisms of action. We will study a total of 350 opossums derived from different genetic stocks; high responders to saturated fat and cholesterol diet, low responders to the same diet, and two other previously uncharacterized genetic stocks. All animals will be bled while feeding the basal maintenance diet and 8, 16 and 24 weeks after feeding one of five diets differing in amounts and types of fat and in cholesterol levels. The first specific aim is to determine lipoprotein phenotypes in plasma samples taken from each animal while consuming the basal diet, and periodically during 24 weeks while consuming one of the challenge diets. Lipoprotein phenotypes will be total cholesterol determined using nondenaturing gradient gel electrophoresis. The results will enable us to determine whether, for some stocks but not others, significant changes in lipoprotein phenotypes are attributable to increases in either of two types of fat (polyunsaturated and saturated) or in cholesterol. The second specific aim is to measure extent and severity of atherosclerotic lesions in all animals and to determine their relationship with time-weighted or aggregate lipoprotein phenotypes. Animals will necropsied after the last (24 week) blood sampling in order to quantify atherosclerotic lesions. The results will enable us to determine whether aspects of lipoprotein phenotypes (including cholesterol levels and particle sizes for the two major types of lipoprotein, very low density plus low density lipoprotein and high density lipoprotein) are associated with extent and severity of lesions. Previous results indicating genetic control of responder phenotype and of high density lipoprotein levels suggest the exciting potential of the opossum model in determining genetic and environmental factors relevant to cardiovascular disease.

该项目的最终目标是建立实验室负鼠， 单层家族，是确定效果的独特模型 饮食和基因型关于脂蛋白表型和开发 动脉粥样硬化。 结合项目5和6项目4将有助于 确定控制饮食反应能力并确定的特定基因 他们的作用机制。 我们将总共研究350个负鼠 源自不同的遗传库存；高响应者对饱和脂肪 和胆固醇饮食，低反应者对同一饮食以及另外两个 以前未表征的遗传库存。 所有动物都会流血 在喂食基础维持饮食和8、16和24周之后 喂食五种饮食中的一种，脂肪的含量和类型不同， 胆固醇水平。 第一个具体目的是确定脂蛋白 从每只动物中采集的血浆样品中的表型，同时消耗 基础饮食，并在24周内定期消耗其中一种 挑战饮食。 脂蛋白表型将是总胆固醇 使用非核梯度凝胶电泳确定。 结果 将使我们能够确定某些股票（而不是其他股票）是否确定 脂蛋白表型的重大变化可归因于 两种类型的脂肪中的任何一种（多不饱和和饱和）增加 或胆固醇。 第二个具体目的是衡量范围和 所有动物中动脉粥样硬化病变的严重程度，并确定它们 与时间加权或聚集脂蛋白表型的关系。 在最后（24周）取样后，动物将被尸检 量化动脉粥样硬化病变。 结果将使我们能够 确定脂蛋白表型的各个方面（包括 两种主要类型的胆固醇水平和粒度 脂蛋白，非常低的密度和低密度脂蛋白和高密度 密度脂蛋白）与病变的程度和严重程度有关。 先前的结果表明响应者表型的遗传控制和 高密度脂蛋白水平表明 负鼠模型确定遗传和环境因素相关 患心血管疾病。