Köchl S, Fresser F, Lobentanz E, Baier G, Utermann G
Institute for Medical Biology and Human Genetics, University of Innsbruck, Austria.
Blood. 1997 Aug 15;90(4):1482-9.
Lipoprotein(a) [Lp(a)], which has been shown to interact with fibrin(ogen) and other components of the blood clotting cascade, is a major independent risk factor for atherothrombotic disease in humans. The physiological function(s) of Lp(a), as well as the precise mechanism(s) by which high plasma levels of Lp(a) increase risk are unknown. Identification of further potential apo(a)-protein ligands may be crucial to illuminate apo(a)'s function(s) and pathophysiological properties. We used the repetitive apo(a) kringle IV type 2, which is variable in number in apo(a), to screen a human liver cDNA library by the yeast two-hybrid interaction trap system. Among 11 positive clones that emerged from the screen, eight clones were identified as beta-2 glycoprotein I and one as fibronectin. Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically expressed apo(a). The apo(a)-beta2-glycoprotein I interaction indicates new potential roles for Lp(a) in fibrinolysis and autoimmunity.
脂蛋白(a)[Lp(a)]已被证明可与纤维蛋白(原)及凝血级联反应的其他成分相互作用，是人类动脉粥样硬化血栓形成疾病的主要独立危险因素。Lp(a)的生理功能以及血浆Lp(a)水平升高增加风险的确切机制尚不清楚。鉴定更多潜在的载脂蛋白(a)蛋白配体可能对阐明载脂蛋白(a)的功能和病理生理特性至关重要。我们使用在载脂蛋白(a)中数量可变的重复载脂蛋白(a)kringle IV 2型，通过酵母双杂交相互作用捕获系统筛选人肝脏cDNA文库。从筛选出的11个阳性克隆中，8个克隆被鉴定为β2糖蛋白I，1个为纤连蛋白。免疫共沉淀实验证实，β2糖蛋白I与apo(a)/Lp(a)在人血浆和异位表达apo(a)的COS-1细胞培养上清液中相互作用。载脂蛋白(a)-β2糖蛋白I相互作用表明Lp(a)在纤维蛋白溶解和自身免疫中具有新的潜在作用。
