PLASMA LIPOPROTEINS BY 1H NMR SPECTROSCOPY

通过 1H NMR 光谱测定血浆脂蛋白

• 批准号: 3361813
• 负责人: JAMES D OTVOS
• 金额: $ 10.7万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3361813
• 关键词: apolipoproteins; blood chemistry; blood lipoprotein; cardiovascular disorder diagnosis; cholesterol; early diagnosis; high density lipoproteins; human subject; low density lipoprotein; nuclear magnetic resonance spectroscopy; protein structure; very low density lipoprotein

The proposed research is aimed at continuing the development of a promising new analytical method that uses proton NMR spectroscopy to simultaneously quantify the concentrations of all of the major lipoproteins in plasma (chylomicrons, VLDL, LDL, HDL), plus determine their subspecies distributions. The accurate identification of individuals at risk for coronary heart disease (CHD) is a high priority in the national effort to combat this disease. Markers of CHD risk in widespread use for population screening are those that can be measured relatively simply and inexpensively. These include total plasma cholesterol, triglyceride, and HDL- and LDL-cholesterol. Initial assignment of CHD risk is currently made on the basis of total cholesterol level; HDL- and LDL-cholesterol measurements are only recommended for those in the moderate and high risk groups: This stepwise approach has several deficiencies which stem from the significant analytical errors associated with laboratory cholesterol and lipoprotein measurements. The new NMR method of lipoprotein analysis has the advantage of supplying an individual's complete lipoprotein profile all at once, using a procedure that is fast, simple, and capable of being completely automated. The basic information is provided by a single proton NMR spectrum of nonfasting plasma, which is then subjected to computer lineshape analysis. Additional research is needed to optimize the methodology used to derive this information, explore the potential of extracting from the spectrum additional information of clinical relevance, and document the relationship of NMR-derived lipoprotein levels to those measured by standard methods. The specific objectives of the research are to 1) determine the best computational approach(es) to extracting the maximum amount of information about lipoprotein levels from the plasma NMR spectrum, 2) determine the maximum resolving power of the NMR method in terms of its ability to quantify lipoprotein subspecies and Lp(a), 3) determine the influence of lipoprotein lipid compositional heterogeneity on the accuracy of the analysis by investigating the thermal profiles of LDL and HDL subspecies of defined lipid and fatty acid composition, and 4) compare NMR-derived lipoprotein concentrations and subspecies distributions with those determined by other chemical and physical methods of analysis.

拟议的研究旨在继续发展一种 有前途的新分析方法，使用质子核磁共振光谱， 同时量化所有主要的 血浆中的脂蛋白（乳糜微粒、VLDL、LDL、HDL），加上测定 亚种分布。 精准识别 冠心病（CHD）高危人群是一个高度优先事项 在国家抗击这种疾病的努力中。 冠心病风险的标志物 广泛用于人群筛查的是那些可以测量的 相对简单和便宜。 其中包括血浆总量 胆固醇、甘油三酯和HDL-和LDL-胆固醇。 初始 冠心病风险的分配目前是根据总的 胆固醇水平; HDL-和LDL-胆固醇测量仅 推荐给那些在中度和高风险群体：这 逐步的方法有几个缺陷， 与实验室胆固醇相关的显著分析错误， 脂蛋白测量。 新的核磁共振脂蛋白分析方法， 提供个体的完整脂蛋白谱的优点 一次完成，使用一个快速，简单， 完全自动化。 基本信息由一个 非空腹血浆的质子NMR谱，然后对其进行 计算机线形分析 需要进一步的研究来优化 用于获得这些信息的方法，探索潜在的 从光谱中提取临床的额外信息 相关性，并记录NMR衍生脂蛋白 这些水平是通过标准方法测量的。 的具体目标 研究的目的是：1）确定最佳计算方法（ES） 最大限度地提取脂蛋白水平的信息 从等离子体NMR光谱，2）确定最大分辨能力 NMR方法定量脂蛋白的能力 亚种和Lp（a），3）确定脂蛋白脂质的影响 成分异质性对分析的准确性， 研究定义的LDL和HDL亚种的热分布， 脂质和脂肪酸组成，以及4）比较NMR衍生的脂蛋白 浓度和亚种分布， 其他化学和物理分析方法。