de la Peña-Díaz A, Cardoso-Saldaña G, Zamora-González J, Barinagarrementeria F, Izaguirre R, Loyau S, Anglés-Cano E
Instituto Nacional de Cardiología Ignacio Chávez, México.
Eur J Clin Invest. 2003 Feb;33(2):99-105. doi: 10.1046/j.1365-2362.2003.01114.x.
Lp(a), a major cardiovascular risk factor, contains a specific apolipoprotein, apo(a), which by virtue of structural homology with plasminogen inhibits the formation of plasmin, the fibrinolytic enzyme. A number of clinical reports support the role of Lp(a) as a cardiovascular or cerebral risk factor, and experimental data suggest that it may contribute to atherothrombosis by inhibiting fibrinolysis.
A well-characterized model of a fibrin surface and an apo(a)-specific monoclonal antibody were used to develop a functional approach to detect pathogenic Lp(a). The assay is based on the competitive binding of Lp(a) and plasminogen for fibrin, and quantifies fibrin-bound Lp(a). High Lp(a) binding to fibrin is correlated with decreased plasmin formation. In a transversal case-control study we studied 248 individuals: 105 had a history of ischaemic cardiopathy (IC), 52 had cerebro-vascular disease (CVD) of thrombotic origin, and 91 were controls.
The remarkably high apo(a) fibrin-binding in CVD (0.268 +/- 0.15 nmol L-1) compared with IC (0.155 +/- 0.12 nmol L-1) suggests the existence of peculiar and poorly understood differences in pro- or anti-thrombotic mechanisms in either cerebral and/or coronary arteries.
Our results demonstrated that Lp(a) fibrin-binding and small Apo(a) isoforms are associated with athero-thrombotic disease.
脂蛋白(a)[Lp(a)]是一种主要的心血管危险因素，含有一种特殊的载脂蛋白apo(a)，该载脂蛋白由于与纤溶酶原结构同源，可抑制纤溶酶（一种纤维蛋白溶解酶）的形成。许多临床报告支持Lp(a)作为心血管或脑血管危险因素的作用，实验数据表明它可能通过抑制纤维蛋白溶解而促进动脉粥样硬化血栓形成。
利用一个特征明确的纤维蛋白表面模型和一种apo(a)特异性单克隆抗体，开发一种检测致病性Lp(a)的功能方法。该检测基于Lp(a)和纤溶酶原对纤维蛋白的竞争性结合，并对与纤维蛋白结合的Lp(a)进行定量。Lp(a)与纤维蛋白的高结合与纤溶酶形成减少相关。在一项横向病例对照研究中，我们研究了248名个体：105人有缺血性心脏病（IC）病史，52人有血栓形成性脑血管疾病（CVD），91人为对照组。
与IC组（0.155±0.12 nmol/L）相比，CVD组apo(a)与纤维蛋白的结合显著更高（0.268±0.15 nmol/L），这表明在脑动脉和/或冠状动脉的促血栓形成或抗血栓形成机制中存在特殊且尚未完全了解的差异。
我们的结果表明，Lp(a)与纤维蛋白的结合以及小的Apo(a)异构体与动脉粥样硬化血栓形成疾病相关。
