Lipoprotein Density Profiling for Clinical Studies

用于临床研究的脂蛋白密度分析

• 批准号: 7465910
• 负责人: RONALD D MACFARLANE
• 金额: $ 28.72万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465910
• 关键词: Arts; Blood; Cardiovascular Diseases; Cardiovascular system; Characteristics; Chemistry; Class; Classification; Clinical; Clinical Research; Collaborations; Complex; Control Groups; Coronary; Coronary artery; Coupled; Data; Density Gradient Centrifugation; Development; Early Diagnosis; Edetic Acid; Goals; Gold; Health; High Density Lipoproteins; Individual; Ions; LDL Cholesterol Lipoproteins; Lipids; Lipoprotein (a); Lipoprotein (a-); Lipoproteins; Measures; Metals; Methodology; Methods; Molecular; Participant; Particle Size; Patients; Pilot Projects; Pliability; Progress Reports; Public Health; Recovery; Resolution; Risk; Screening procedure; Standards of Weights and Measures; Statistical Methods; Statistically Significant; Stents; Testing; Translational Research; Work; base; cardiovascular disorder risk; cohort; density; experience; immunoreactivity; implantation; in vivo; innovation; low density lipoprotein inhibitor; novel; particle; restenosis; sedimentation equilibrium; solute; success

DESCRIPTION (provided by applicant): The ability to identify individuals at risk for cardiovascular disease (CVD) is of paramount importance with respect to both early detection and control. The 'quality' of lipoprotein particles circulating in the blood exerts a significant influence on CVD. One measure of this 'quality' is its density, the gold standard parameter for characterizing the major lipoprotein classes and their subclasses. The long-term goal is to have in place a general method for characterizing lipoprotein subclasses to accurately distinguish between subject groups and controls in a clinical study. The first specific aim is to develop a comprehensive, accurate and reproducible method for measuring a lipoprotein density profile based on sedimentation equilibrium density-gradient ultracentfiugation. Development of an array of secondary lipoprotein density profiling methods is the focus of the second specific aim. Coupled with this project is a method to recover specific lipoprotein subclasses for a more detailed characterization of structural and functional features. The third specific aim has a statistical analysis and a clinical component. Data derived from the lipoprotein density profile are used to classify subjects and controls using modern statistical methods for classification analysis. The analysis will be developed and applied to a clinical study on atherogenic HDL to determine which statistically-significant parameters are contained in the lipoprotein density profile. The methodology developed from the first three specific aims will be applied to the fourth specific aim, a clinical study to identify lipoprotein subclasses associated with in-stent restenosis following implantation of a bare metal stent. Lipoproteins are active participants in cardiovascular disease and health. They are also internal probes of the circulatory system at the molecular level. The delicate in vivo interplay between lipoprotein subclasses is reflected in features of the lipoprotein density profile, the focus of this proposal. PUBLIC HEALTH RELEVANCE This project is a contribution to identifying those individuals with normal HDL and LDL cholesterol levels who are actually at risk for developing for cardiovascular disease. Using the same methodology, individuals at risk for premature restenosis following coronary stenting will be identified.

描述（由申请人提供）：识别患有心血管疾病风险（CVD）的个体的能力对于早期检测和控制都至关重要。血液中循环的脂蛋白颗粒的“质量”对CVD产生了重大影响。这种“质量”的一种度量是其密度，这是表征主要脂蛋白类及其子类的金标准参数。长期目标是建立一种表征脂蛋白亚类的一般方法，以准确区分临床研究中的受试者和对照。第一个具体目的是开发一种基于沉降平衡密度梯度超富施ugation的全面，准确和可再现的方法，用于测量脂蛋白密度谱。开发一系列二级脂蛋白密度分析方法是第二个特定目的的重点。结合该项目是一种恢复特定脂蛋白亚类的方法，以更详细地表征结构和功能功能。第三个特定目标具有统计分析和临床成分。源自脂蛋白密度分布的数据用于使用现代统计方法进行分类分析对受试者和对照进行分类。该分析将被开发并应用于有关动脉粥样硬化HDL的临床研究，以确定脂蛋白密度谱中包含哪些统计学意义的参数。从前三个特定目的开发的方法将应用于第四个特定目标，这是一项临床研究，以鉴定植入裸金属支架后与支架内再狭窄相关的脂蛋白亚类。脂蛋白是心血管疾病和健康的积极参与者。它们也是分子水平循环系统的内部探针。脂蛋白亚类之间微妙的体内相互作用反映在脂蛋白密度谱的特征中，这是该建议的重点。公共卫生相关性这个项目是为了确定那些患有正常HDL和LDL胆固醇水平的人，他们实际上有患心血管疾病的风险。使用相同的方法，将确定有冠状动脉支架后过早再狭窄的人。