HDL STRUCTURE AND METABOLISM IN A WOMEN WITH LOW HDL

HDL 水平低的女性的 HDL 结构和代谢

• 批准号: 2214355
• 负责人: GRETCHEN P EBERHART
• 金额: $ 3.53万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-12-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2214355
• 关键词: HDL; STRUCTURE; METABOLISM; WOMEN; LOW

The importance of high density lipoproteins (HDL) in protecting against the development of atherosclerosis has been well established. While the mechanism by which HDL protects against atheroma formation is presumed to be secondary to it' s role in reverse cholesterol transport, the structural requirements for that function are uncertain. Genetic disorders resulting in abnormal HDL particles may shed light on this question. We have identified a 48 year old woman with HDL cholesterol levels in the 0-13 mg/dl range. Using the polymerase chain reaction, we have tentatively identified a mutation in her apo A-I gene. Surprisingly, despite her extremely low HDL cholesterol levels, she has no evidence of CAD. The exploration of the relevance of this putative mutation to HDL function may illuminate aspects of the A-I apoprotein's structure/function relationships, and aid in the understanding of the protective effect of HDL against coronary artery disease. We plan to investigate HDL particle structure in the proband by immunoaffinity column chromatography, SDS polyacrylamide gel electrophoresis, and non-denaturing gradient polyacrylamide gel electrophoresis. Apo A-I structure will be assessed by two dimensional gel electrophoresis. The apo A-I gene will be assessed with techniques including the polymerase chain reaction, Southern blotting, creating and screening a genomic DNA library, and DNA sequencing. Metabolism of apo A-I will be studied by an endogenous labeling protocol with trideuterated leucine as the tracer.

高密度脂蛋白 (HDL) 在预防疾病方面的重要性 动脉粥样硬化的发展已得到充分证实。 虽然 HDL 预防动脉粥样硬化形成的机制被推测 其在逆转胆固醇转运中的作用是次要的 该功能的结构要求是不确定的。 遗传 导致 HDL 颗粒异常的疾病可能会揭示这一点 问题。 我们发现一名 48 岁女性的 HDL 胆固醇水平 0-13 毫克/分升范围。 利用聚合酶链式反应，我们有 初步鉴定出她的 apo A-I 基因发生突变。 出奇， 尽管她的高密度脂蛋白胆固醇水平极低，但没有证据表明她 计算机辅助设计。 探索这种假定突变与 HDL 的相关性 功能可能阐明 A-I 脱辅基蛋白的各个方面 结构/功能关系，并帮助理解 HDL 对冠状动脉疾病的保护作用。 我们计划通过以下方式研究先证者的 HDL 颗粒结构： 免疫亲和柱层析，SDS聚丙烯酰胺凝胶 电泳、非变性梯度聚丙烯酰胺凝胶 电泳。 Apo A-I 结构将通过二维评估 凝胶电泳。 apo A-I 基因将通过技术进行评估 包括聚合酶链式反应、Southern blotting、创建和 筛选基因组 DNA 文库和 DNA 测序。 载脂蛋白的代谢 A-I 将通过三氘代内源标记方案进行研究 亮氨酸作为示踪剂。