Study on the physiological and pathological significances of lipoprotein(a).

1)日本Lp（a）测定方法及正常值。本文对酶联免疫吸附法（ELISA）测定脂蛋白（a）试剂盒进行了评价，并对纤溶酶原对测定的免疫干扰进行了研究。通过这种检测方法获得的结果进行了比较，与我们的多克隆ELISA方法。采用该方法检测了1513名日本健康人的血清Lp（a）。2）日本健康人和冠心病患者的Lp（a）表型频率。健康日本人的Lp（a）水平分布、平均值和中位数以及Lp（a）表型和等位基因频率与欧洲人的结果无显著差异，而与其他亚洲人群有显著差异。冠心病组Lp（a）等位基因频率与健康对照组无显著性差异。Lp（a）水平在患者中高于同表型的健康人。3）作为急性期反应物的变化。虽然IL-6、CRP和α_1-抗胰蛋白酶分别在发病后1-2天、3天和4-5天达到高峰，但心肌梗死组和手术组Lp（a）水平的峰值时间有一定程度的延迟。研究Lp（a）水平的瞬时增加作为apo（a）异构体的函数，优先含有高分子量apo（a）异构体的高密度Lp（a）颗粒比低密度Lp（a）颗粒增加更多。4）Lp（a）与止血过程中的临床参数之间的关系。测定了健康人和冠心病患者血浆Lp（a）、达特、t-PA、派-1、t-PA-派-1复合物和PIC的浓度。健康组Lp（a）水平与PIC值呈显著正相关，而冠心病组Lp（a）水平与PIC值无相关性。提示Lp（a）具有调节凝血纤溶系统的作用，可能干扰冠心病患者的纤溶系统。

1) Lp(a) assay method and normal value in Japan. We evaluated the ELISA kit for Lp(a) determination, and the immunological interference by plasminogen on the assay. Results obtained by this assay method were compared with those by our polyclonal ELISA method. Serum Lp(a) was determined in 1513 healthy Japanese with use of the assay method.2) Lp(a) phenotype frequencies in healthy Japanese and in patients with CAD. The distribution of Lp(a) levels, mean and median values, and Lp(a) phenotype and allele frequencies in healthy Japanese were not significantly different from the results for Europeans, whereas they were significantly different from other Asian populations. The frequencies of Lp(a) alleles in the CAD patients were not significantly different from those in the healthy subjects. Lp(a) levels in the patients were higher than those in the healthy subjects with the same phenotype.3) Change as an acute phase reactant. Although IL-6, CRP and alpha_1-antitrypsin reached the maximal levels 1-2 days, 3 days and 4-5 days after the episodes, respectively, the peak time of Lp(a) levels delayed some extent in myocardial infarction and surgical operated groups. Studying on the transient increases of Lp(a) levels as a function of apo(a) isoforms, the higher density Lp(a) particles preferentially containing high molecular weight apo(a) isoforms were more increased than the lower density Lp(a) particles.4) Relationship between Lp(a) and clinical parameters in the hemostatic process. Plasma concentrations of Lp(a), TAT, t-PA, PAI-1, t-PA-PAI-1 complex and PIC were determined in healthy subjects and in patients with CAD. Lp(a) levels showed a significant positive correlation with PIC values in the healthy group, whereas this correlation was disappeared in the CAD group. These results suggest that Lp(a) has the potential to regulate the coagulation-fibrinolytic system and that it may interfere with the fibrinolytic system in patients with CAD.