Vucković Biljana, Derić Mirjana
Klinicki centar Novi Sad, Novi Sad, Institut za laboratorijsku medicinu.
Med Pregl. 2007 Jan-Feb;60(1-2):37-41. doi: 10.2298/mpns0702037v.
It is well known that numerous mechanisms of thrombogenesis can participate in every stage of atherosclerotic disease. The discovery of Lp(a) lipoprotein and its structural similarity with plasminogen suggests another pathogenic link between atherogenesis and thrombogenesis.
SOME CHARACTERISTICS OF LP(A) LIPOPROTEIN: This lipoprotein is present in the whole human population in a wide range of plasma concentrations. It has numerous different isoforms. Its synthesis occurs in the liver, but it is practically metabolically independent from other lipoproteins. Today, Lp(a) lipoprotein is considered to be an independent risk factor for heart and brain ischemic disease.
The primary role of the fibrinolytic mechanism is to prevent thrombus Jormation during circulation and to remove already formed ones. Plasmin has a central role in this process, due to the inactive proenzyme plasminogen. Its basic activators are tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA). The most important inhibitors of plasminogen are alpha2-antiplasmin and plasminogen activator inhibitors 1 and 2 (PA-1 and PAI-2). Structural similarity of Lp(a) and plasminogen The apo(a) and plasminogen genes are very closely linked on the long arm of chromosome 6. Because of that they are structuraly very similar and they have a cross immunological reactivity. Their common elements are so-called "kringle" structures. The key difference in structure of Lp(a) and plasminogen is replacement of Arg with Ser at position 560. This prevents splitting of apo(a) by plasminogen activators.
LP(A) AND FIBRINOLYSIS: Lp(a) lipoprotein inhibits activation of plasminogen by streptokinase. It is also a competitive inhibitor of plasminogen for its binding to plasminogen receptors. Furthermore, it successfully achieves competitive inhibition of plasminogen for binding to tetranectin and thrombospondin. Also, Lp(a) inhibits activation of transforming growth factor alpha (TGF-alpha). It positively correlates with PAI-1 and it is assumed that it promotes release of tissue factor pathway inhibitor (17FPI) from endothelial cell surfaces.
In regulation of the hemostatic system via apolipoprotein(a) antifibrinolytic effects, Lp(a) lipoprotein ojfers a molecular solution to the link between thrombogenesis and atherogenesis.
众所周知，多种血栓形成机制可参与动脉粥样硬化疾病的各个阶段。脂蛋白（a）[Lp（a）]的发现及其与纤溶酶原的结构相似性提示了动脉粥样硬化形成与血栓形成之间的另一种致病联系。
Lp（a）脂蛋白的一些特征：这种脂蛋白在整个人口中都有存在，血浆浓度范围很广。它有许多不同的同工型。其合成发生在肝脏，但在代谢上实际上独立于其他脂蛋白。如今，Lp（a）脂蛋白被认为是心脏和脑缺血性疾病的独立危险因素。
纤溶机制的主要作用是在循环过程中防止血栓形成，并清除已形成的血栓。由于无活性的酶原纤溶酶原，纤溶酶在这一过程中起核心作用。其主要激活剂是组织型纤溶酶原激活剂（t-PA）和尿激酶型纤溶酶原激活剂（u-PA）。纤溶酶原最重要的抑制剂是α2-抗纤溶酶以及纤溶酶原激活剂抑制剂1和2（PAI-1和PAI-2）。
Lp（a）与纤溶酶原的结构相似性：载脂蛋白（a）[apo（a）]和纤溶酶原基因在6号染色体长臂上紧密相连。因此它们在结构上非常相似，具有交叉免疫反应性。它们的共同元件是所谓的“kringle”结构。Lp（a）和纤溶酶原结构的关键区别在于560位的精氨酸被丝氨酸取代。这阻止了纤溶酶原激活剂对apo（a）的裂解。
Lp（a）与纤溶：Lp（a）脂蛋白抑制链激酶对纤溶酶原的激活。它也是纤溶酶原与纤溶酶原受体结合的竞争性抑制剂。此外，它成功地竞争性抑制纤溶酶原与骨桥蛋白和血小板反应蛋白的结合。而且，Lp（a）抑制转化生长因子α（TGF-α）的激活。它与PAI-1呈正相关，并且推测它促进组织因子途径抑制剂（TFPI）从内皮细胞表面释放。
通过载脂蛋白（a）的抗纤溶作用在止血系统的调节中，Lp（a）脂蛋白为血栓形成与动脉粥样硬化形成之间的联系提供了一种分子解释。
