ANALYSIS OF PLASMA LIPOPROTEINS BY 1H NMR SPECTROSCOPY

通过 1H NMR 光谱分析血浆脂蛋白

• 批准号: 3361815
• 负责人: JAMES D OTVOS
• 金额: $ 9.83万
• 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 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3361815
• 关键词: angiography; apolipoproteins; artery; blood lipoprotein; cholesterol; coronary disorder; density gradient ultracentrifugation; diagnosis quality /standard; early diagnosis; heart disorder diagnosis; high density lipoproteins; human subject; low density lipoprotein; nuclear magnetic resonance spectroscopy; protein structure; questionnaires; rapid diagnosis; very low density lipoprotein

The proposed research is aimed at developing and evaluating the clinical utility of new methodology using H1 NMR spectroscopy to quantitate the levels of the constituent lipoproteins of human blood plasma (VLDL, LDL, HDL). 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 that are in current widespread use for population screening have proven to be of great value in this effort. These include total cholesterol and triglyceride, LDL- and HDL- cholesterol, and apolipoproteins A-1 and B. Accurate measurement of these constituents is a prerequisite for their effective clinical use and continues to be a challenging problem. Our preliminary studies indicate that it is possible in a simple and rapid process to extract the concentrations of VLDL, LDL, and HDL present in an individual's blood from a computer lineshape analysis of the lipid resonances in a H1 NMR spectrum of the plasma. There are still a great number of questions remaining concerning the precise meaning of the data provided by the technique, its accuracy and reproducibility, and its possible clinical uses. The proposed research addresses these questions and has the following as its specific goals; 1) documentation of the NMR spectral relationships between the lipoprotein subspecies that comprise the three broad components (VLDL, LDL, HDL) used in the lineshape analysis, 2) determination of the extent to which variability in subspecies and lipid composition affect the lineshapes and amplitudes at a given temperature of the individual lipoprotein components, 3) optimization of the analytical protocol for NMR plasma lineshape analysis by documenting the influence of factors such as magnetic field strength, temperature, and fitting algorithm on the accuracy of the analysis, 4) determination of the relationships between NMR-derived lipoprotein levels and those provided by lipoprotein lipid and apolipoprotein assays, and 5) evaluation of the potential diagnostic utility of NMR-derived lipoprotein levels by determining their association with CHD as assessed by coronary arteriography.

拟议的研究旨在开发和评估临床 使用 H1 NMR 光谱来定量的新方法的效用 人血浆中脂蛋白成分（VLDL、LDL、 高密度脂蛋白）。 准确识别有冠心病风险的个体 心脏病（CHD）是国家抗击心脏病工作的重中之重 这种病。 目前广泛使用的 CHD 风险标记 事实证明，人口筛查在这项工作中具有巨大价值。 其中包括总胆固醇和甘油三酯、低密度脂蛋白 (LDL) 和高密度脂蛋白 (HDL) 胆固醇、载脂蛋白 A-1 和 B。准确测量这些 成分是其有效临床使用的先决条件 仍然是一个具有挑战性的问题。 我们的初步研究表明 可以通过简单而快速的过程提取 个体血液中 VLDL、LDL 和 HDL 的浓度 H1 NMR 谱中脂质共振的计算机线形分析 的等离子体。 仍有大量问题悬而未决 关于该技术提供的数据的精确含义，其 准确性和再现性及其可能的临床用途。 这 拟议的研究解决了这些问题，并具有以下内容 具体目标； 1) 核磁共振谱关系的记录 脂蛋白亚种包含三种主要成分（VLDL、 LDL、HDL)用于线形分析，2)确定程度 亚种和脂质成分的变异性影响 个体给定温度下的线形和振幅 脂蛋白成分，3) NMR 分析方案的优化 通过记录以下因素的影响进行等离子体线形分析 磁场强度、温度和拟合算法 分析的准确性，4）确定之间的关系 NMR 衍生的脂蛋白水平以及由脂蛋白脂质和 载脂蛋白测定，以及 5) 潜在诊断评估 通过确定 NMR 衍生的脂蛋白水平的关联来利用它们 通过冠状动脉造影评估患有 CHD。