不同位点氧化脂蛋白(a)水平与冠心病的关系研究

项目名称： 不同位点氧化脂蛋白(a)水平与冠心病的关系研究

项目编号： No.30872411

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 汪俊军

作者单位： 中国人民解放军南京军区南京总医院

项目金额： 29万元

中文摘要： 脂蛋白(a)[Lp(a)]中载脂蛋白(a)[apo(a)]和B位点均可被氧化，氧化Lp(a)[Ox-Lp(a)]水平是否可作为一种新的动脉粥样硬化(As)危险因素，与As发生、程度和斑块稳定性是否关联、变化机制，以及具体检测何种位点更有价值等均不清楚。本项目首次提出采用识别apo(a)和B氧化位点的自身抗体建立Ox-Lp(a)检测法，以准确、真实地反映体内Lp(a)氧化状况，同时采用针对氧化apo(a)、B和氧化磷脂的特异抗体建立不同位点Ox-Lp(a)检测法，进行系列临床研究（稳定型、不同时相的不稳定型冠心病，经皮冠状动脉干预等患者），分析apo(a)基因型、脂蛋白相关磷脂酶活性，Ox-Lp(a)自身抗体、循环免疫复合物水平对Ox-Lp(a)水平的作用效果和机制，明确Ox-Lp(a)水平在冠心病中的变化及其机制，准确评价其临床价值，为As性疾病的诊断、防治提供新的途径和理论依据。

中文关键词： 脂蛋白(a)；自身抗体；冠心病；急性冠脉综合症；动脉粥样硬化

英文摘要： We isolated human autoantibodies against oxidized lipoprotein(a) [ox-Lp(a)], which can recognize both apolipoprotein(a) [apo(a)] and apoB epitopes of ox-Lp(a). Simultaneously, a second ELISA using polyclonal antibodies to capture oxidized apoB of Lp(a) was also applied for the serial clinical research. The newly developed enzyme-linked immunosorbent assays (ELISA) for ox-Lp(a) by using human auoantibodies may more accurately reflect the state of lipoprotein(a) [Lp(a)] oxidation in vivo, and may represent a better risk marker for acute coronary syndromes (ACS) and stable coronary artery disease (SCAD) than that using antibodies to capture oxidized apoB. Ox-Lp(a) levels have been found to be present in newborns and children, and increased in rheumatoid arthritis patients with excessive cardiovascular events. Furthermore, elevated ox-Lp(a) levels have been found to be associated with the presence of SCAD and ACS, and with severity of ACS. Increased ox-Lp(a) levels are established as strong risk factors for atherosclerosis, which are closely related to the degree of atherosclerosis and rupture of unstable coronary atherosclerotic plaque. Percutaneous coronary intervention results in acute plasma increases of ox-Lp(a) and Lp(a). βglycoprotein-I might bind Lp(a) or LDL to form complexes in vivo. The βGPI-Lp(a) or βGPI-LDL was increased in coronary artery disease and involved in the presence and development of atherosclerosis. Totally more than 22 papers have been published, among which 9 are SCI papers. The papers of the project have been submitted to academic meetings for many times. The project has won the second science-technology award and provided not only some new approach but also the theory basis for the further study of pathogenesis, clinical diagnosis and treatment of atherosclerosis.

英文关键词： Lipoprotein(a); Autoantibody; Coronary artery disease; Acute coronary syndromes; Atherosclerosis