PLASMA LIPOPROTEINS BY 1H NMR SPECTROSCOPY

通过 1H NMR 光谱测定血浆脂蛋白

• 批准号: 2220943
• 负责人: JAMES D OTVOS
• 金额: $ 10.98万
• 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/2220943
• 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开发一种 一种很有前途的新分析方法，它使用质子核磁共振光谱来 同时量化所有主要污染物的浓度 血浆中的脂蛋白(乳糜粒、极低密度脂蛋白、低密度脂蛋白、高密度脂蛋白)，加上测定 它们的亚种分布。准确地识别出 冠心病(CHD)的高危人群是高度优先考虑的 在国家抗击这种疾病的努力中。冠心病风险的标记物 人口筛查的广泛应用是那些可以测量的 相对简单和便宜。其中包括总血浆 胆固醇、甘油三酯、高密度脂蛋白和低密度脂蛋白。首字母 目前，冠心病风险的分配是基于 胆固醇水平；高密度脂蛋白和低密度脂蛋白的测量只是 推荐给中等和高风险人群：这 循序渐进的方法有几个缺陷，这些缺陷源于 与实验室胆固醇和 脂蛋白测量。新的分析脂蛋白的核磁共振方法 提供个人完整的脂蛋白图谱的优势 一下子，使用一个快速、简单并能够 完全自动化。基本信息由单个 非禁食等离子体的质子核磁共振谱 计算机线型分析。还需要更多的研究来优化 用于获取这些信息的方法，探索潜在的 从光谱中提取临床的附加信息 相关性，并记录核磁共振衍生的脂蛋白之间的关系 与用标准方法测量的水平相当。具体目标 研究的目的是：1)确定最佳计算方法 以最大限度地提取有关脂蛋白水平的信息 根据等离子体核磁共振谱，2)确定最大分辨率 核磁共振方法在定量脂蛋白能力方面的优势 亚种和Lp(A)，3)决定脂蛋白脂质的影响 成分异质性对分析准确性的影响 低密度脂蛋白和高密度脂蛋白亚型热谱的研究 脂肪和脂肪酸组成，以及4)比较核磁共振衍生的脂蛋白 浓度和亚种分布与由 其他化学和物理分析方法。