ANALYSIS OF PLASMA LIPOPROTEINS BY 1H NMR SPECTROSCOPY

这项拟议的研究旨在开发和评估临床 利用核磁共振氢谱定量测定蛋白质的新方法 人血浆组成脂蛋白(极低密度脂蛋白、低密度脂蛋白、 高密度脂蛋白)。准确识别冠脉高危人群 心脏病(CHD)是国家努力抗击的一个高度优先事项 这种病。目前广泛使用的冠心病风险标志物 事实证明，人口筛查在这一努力中具有重要价值。 这些指标包括总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白。 胆固醇、载脂蛋白A-1和载脂蛋白B。 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 在一个简单而快速的过程中提取 个体血液中极低密度脂蛋白、低密度脂蛋白和高密度脂蛋白的浓度 H1核磁共振谱中脂类共振的计算机线型分析 血浆的含量。仍然有大量的问题有待解决 关于该技术提供的数据的准确含义，其 准确度和重复性及其可能的临床应用。这个 拟议的研究解决了这些问题，并提出了以下内容 具体目标：1)记录核磁共振波谱之间的关系 构成三个主要成分(极低密度脂蛋白， 低密度脂蛋白、高密度脂蛋白)在线形分析中使用，2)确定程度 亚种和脂类组成的变异性会影响 在个体给定温度下的线形和幅度 脂蛋白组分，3)核磁共振分析方法的优化 通过记录诸如以下因素的影响来分析等离子体线形 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 核磁共振衍生的脂蛋白水平以及由脂蛋白脂质和 载脂蛋白检测，以及5)潜在诊断的评估 通过确定它们的关联性来确定核磁共振衍生脂蛋白水平的实用性 冠状动脉造影术诊断为冠心病。

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.