卵磷脂胆固醇酰基转移酶活性与动脉粥样硬化危险关系研究

项目名称： 卵磷脂胆固醇酰基转移酶活性与动脉粥样硬化危险关系研究

项目编号： No.81472035

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 董军

作者单位： 北京医院

项目金额： 80万元

中文摘要： 大量流行病学研究证明，HDL胆固醇（HDL-C）降低是动脉粥样硬化性心血管病（CVD）的重要危险因素。HDL-C降低多伴有甘油三酯升高和小颗粒脂蛋白增多（血脂三联症），共同造成动脉粥样硬化危险。HDL的主要功能之一是促进胆固醇逆向转运（RCT），卵磷脂胆固醇酰基转移酶（LCAT）是HDL代谢和RCT中的关键酶，LCAT活性一直被认为是重要的动脉粥样硬化保护因素。但多年来这种保护作用未能被证实，有关LCAT活性的人体研究甚少，且结果不一。主要原因是现有LCAT活性测定方法不成熟，对LCAT活性影响因素和生物学作用认识有限。本项目以建立可靠的LCAT活性测定方法为基础，研究生理状态下LCAT活性可能抑制因素及其作用程度，尝试证明LCAT活性的动脉粥样硬化保护作用，提出血脂三联症共存关系及其促动脉粥样硬化作用的新机制；同时为CVD防治提供有潜在应用价值的危险预示指标。

中文关键词： 动脉粥样硬化；卵磷脂胆固醇酰基转移酶；活性测定；危险分析

英文摘要： Epidemiological studies have demonstrated that low high-density lipoprotein cholesterol(HDL-C) is an independent risk factor for atherosclerotic cardiovascular diseases(CVD). However, efforts to increase HD-C did not achieve consistent results. Low HDL-C is often accompanied by high serum triglycerides (TG) and accumulation of small lipoprotein particles. One of the important functions of HDL is its reverse cholesterol transport (RCT). Lecithin-cholesterol acylthansferase (LCAT) is the key enzyme in HDL metabolism and RCT. Although LCAT activity has long been regarded as a protective factor for atherosclerosis, there are few population based studies and the results are controversial. The main reason is that LCAT activities measured by the current methods did not reflect true activities in vivo, and the knowledge about LCAT activity and cofactors are limited. The purpose of this study is to set up a reliable method for measurement of LCAT activity. Based on this method, to investigate the possible inhibition factors under physiological states, demonstrate the protective effects of LCAT on atheroslerosis, and explore the new mechanism of atheroslerotic lipoprotein profile in the development of atheroslerosis. The newly developed LCAT activity method will provide a potentially useful tool for risk accessment of atherosclerosis.

英文关键词： Atherosclerosis;LCAT;Determination of activity;risk analysis