Armstrong V W
Abteilung Klinische Chemie, Universitätsklinikum, Göttingen.
Ther Umsch. 1990 Jun;47(6):475-81.
The lipoprotein Lp(a) is a cholesterol-rich plasma lipoprotein from the density fraction 1.06-1.21 g/ml. Numerous clinical and epidemiological studies have revealed a strong correlation between high plasma Lp(a) concentrations and the incidence of coronary heart disease. Furthermore, the Lp(a)-specific protein apo(a) has been detected in atherosclerotic lesions. Lp(a) is essentially an LDL-like lipoprotein particle to which the glycoprotein apo(a) is attached through a disulfide bridge with apo B-100. The elucidation of the amino acid sequence of apo(a) revealed a high homology to specific regions of human plasminogen. The latter consists of five tandemly arranged kringle domains followed by a C-terminal trypsin-like protease region. Apo(a) is composed of a large number of kringle domains, all highly homologous to kringle IV of plasminogen, followed by a kringle V-like protease-domain. The lipoprotein Lp(a), therefore, combines structural elements of both the lipoprotein and coagulation systems. In contrast to plasminogen, Lp(a) cannot be activated by TPA, streptokinase or urokinase to give proteolytic activity. However, in vitro studies have shown that Lp(a) can both inhibit endothelial cell induced fibrinolysis and can also bind to plasmin modified fibrin. These findings provide a pathobiochemical basis for the involvement of Lp(a) in atherosclerotic and thrombotic processes. The function of this lipoprotein is, however, still unclear.
脂蛋白Lp(a)是一种富含胆固醇的血浆脂蛋白,密度为1.06 - 1.21 g/ml。众多临床和流行病学研究表明,血浆Lp(a)浓度升高与冠心病发病率之间存在密切关联。此外,在动脉粥样硬化病变中已检测到Lp(a)特异性蛋白载脂蛋白(a)[apo(a)]。Lp(a)本质上是一种类似低密度脂蛋白(LDL)的脂蛋白颗粒,糖蛋白apo(a)通过二硫键与载脂蛋白B-100相连。对apo(a)氨基酸序列的阐明揭示了其与人类纤溶酶原特定区域的高度同源性。后者由五个串联排列的kringle结构域和一个C端胰蛋白酶样蛋白酶区域组成。Apo(a)由大量kringle结构域组成,所有这些结构域都与纤溶酶原的kringle IV高度同源,随后是一个类似kringle V的蛋白酶结构域。因此,脂蛋白Lp(a)结合了脂蛋白和凝血系统的结构元件。与纤溶酶原不同,Lp(a)不能被组织型纤溶酶原激活剂(TPA)、链激酶或尿激酶激活而产生蛋白水解活性。然而,体外研究表明,Lp(a)既能抑制内皮细胞诱导的纤维蛋白溶解,也能与纤溶酶修饰的纤维蛋白结合。这些发现为Lp(a)参与动脉粥样硬化和血栓形成过程提供了病理生化基础。然而,这种脂蛋白的功能仍不清楚。