Pekelharing H L, Kleinveld H A, Duif P F, Bouma B N, van Rijn H J
Department of Clinical Chemistry, University Hospital Utrecht, The Netherlands.
Blood Coagul Fibrinolysis. 1996 Sep;7(6):641-9. doi: 10.1097/00001721-199609000-00010.
Lipoprotein (a) [Lp(a)], and to a lesser extent low-density lipoprotein (LDL), have been shown to compete with plasminogen for binding to the extracellular matrix (ECM). Evidence exists that modification of lipoproteins alters their atherogenic properties. Therefore in the present study the effect of modifying Lp(a) and LDL by copper-induced in vitro oxidation on their ability to compete with plasminogen for binding to the ECM was studied. Oxidation of Lp(a) resulted in increased competitiveness for plasminogen binding. This effect was dependent on the Lp(a) concentration used, as well as the extent of oxidation. In the highest Lp(a) concentration used (100 nmol/l apo B100), inhibition of plasminogen binding was further increased with almost 30% compared with native Lp(a). In contrast, oxidation of LDL resulted in an additional inhibition of plasminogen binding of about 10% at all concentrations used. In separate experiments Lp(a) and LDL were modified by neuraminidase treatment. After desialylation a strong tendency for better competitiveness of Lp(a) was observed. Desialylation of LDL had no effect on its ability to compete with plasminogen for binding to the ECM. Modification of the additional and distinguishing apolipoprotein [i.e. apo(a)] in Lp(a) by oxidation and desialylation most likely explains the difference in behaviour of Lp(a) and LDL. It is concluded that modification by oxidation, and to a lesser extent desialylation, increases the anti-fibrinolytic potential of Lp(a).
脂蛋白(a)[Lp(a)]，以及程度稍轻的低密度脂蛋白(LDL)，已被证明可与纤溶酶原竞争结合细胞外基质(ECM)。有证据表明脂蛋白的修饰会改变其致动脉粥样硬化特性。因此，在本研究中，研究了通过铜诱导的体外氧化修饰Lp(a)和LDL对它们与纤溶酶原竞争结合ECM能力的影响。Lp(a)的氧化导致其与纤溶酶原结合的竞争力增强。这种效应取决于所用Lp(a)的浓度以及氧化程度。在所用的最高Lp(a)浓度(100 nmol/l载脂蛋白B100)下，与天然Lp(a)相比，纤溶酶原结合的抑制进一步增加了近30%。相比之下，LDL的氧化在所有使用浓度下导致纤溶酶原结合额外抑制约10%。在单独的实验中，Lp(a)和LDL通过神经氨酸酶处理进行修饰。去唾液酸化后，观察到Lp(a)具有更强竞争力的强烈趋势。LDL的去唾液酸化对其与纤溶酶原竞争结合ECM的能力没有影响。通过氧化和去唾液酸化对Lp(a)中额外的和独特的载脂蛋白[即载脂蛋白(a)]进行修饰，很可能解释了Lp(a)和LDL行为的差异。得出的结论是，氧化修饰以及程度稍轻的去唾液酸化增加了Lp(a)的抗纤溶潜力。
