Chapman M J, Huby T, Nigon F, Thillet J
INSERM Unité 321, Unité de Recherche sur les Lipoprotéines et l'Athérogénèse, Hôpital de la Pitié, Paris, France.
Atherosclerosis. 1994 Oct;110 Suppl:S69-75. doi: 10.1016/0021-9150(94)05385-v.
Substantial experimental evidence now implicates lipoprotein (a) as an independent risk factor for premature cardiovascular disease. Both plasma Lp(a) levels and apo(a) phenotype are strong predictors of risk for ischaemic heart disease. The accumulation of apo(a) in vascular wall tissue and in atherosclerotic plaques and the potential inhibition of fibrinolysis by Lp(a) underlie the enhanced risk of premature cardiovascular disease associated with this cholesterol-rich particle. Recent studies of the capacity of purified Lp(a) isoforms to inhibit fibrinolysis in an in vitro system have revealed that small isoforms of Lp(a) (< or = 500 kDa) are efficient inhibitors of plasminogen activation and bind with high affinity to fibrin. Conversely, large isoforms exert little or no inhibitory effect in this system (> 500 kDa). These data suggest that the potential, high affinity interaction of Lp(a) particles containing small isoforms with fibrin introduces a new, third dimension to the atherothrombotic risk associated with these cholesterol-rich particles.
目前大量实验证据表明，脂蛋白(a)是早发性心血管疾病的独立危险因素。血浆Lp(a)水平和载脂蛋白(a)表型都是缺血性心脏病风险的强预测指标。载脂蛋白(a)在血管壁组织和动脉粥样硬化斑块中的积聚，以及Lp(a)对纤维蛋白溶解的潜在抑制作用，是与这种富含胆固醇的颗粒相关的早发性心血管疾病风险增加的基础。最近关于纯化的Lp(a)异构体在体外系统中抑制纤维蛋白溶解能力的研究表明，小异构体的Lp(a)(≤500 kDa)是纤溶酶原激活的有效抑制剂，并与纤维蛋白具有高亲和力结合。相反，大异构体在该系统中几乎没有抑制作用(>500 kDa)。这些数据表明，含有小异构体的Lp(a)颗粒与纤维蛋白的潜在高亲和力相互作用为与这些富含胆固醇的颗粒相关的动脉粥样硬化血栓形成风险引入了一个新的、第三个维度。
