High plasma levels of apo(a) fragments in Caucasians and African-Americans with end-stage renal disease: implications for plasma Lp(a) assay.
High plasma levels of apo(a) fragments in Caucasians and African-Americans with end-stage renal disease: implications for plasma Lp(a) assay.
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患有终末期肾病的白种人和非裔美国人中 apo(a) 片段的血浆水平较高：对血浆 Lp(a) 测定的影响。
DOI：
10.1111/j.1399-0004.1997.tb04358.x
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发表时间：
1997
影响因子：
3.5
通讯作者：
Hobbs,HH
中科院分区：
文献类型：
--
作者：
Mooser,V;Marcovina,SM;Wang,J;Hobbs,HH
载脂蛋白（a）[apo（a）]是一种血浆糖蛋白，由于其N端称为kringle（K）4的串联富含半胱氨酸重复序列的数量差异，其大小高度多态。大多数血浆载脂蛋白（a）与载脂蛋白B-100共价连接，并作为脂蛋白（a）[Lp（a）]的一部分循环。一部分载脂蛋白（a）在循环中不含脂蛋白。几乎所有的游离apo（a）都由含有来自N末端区域的可变数量的K4重复序列的片段组成。之前我们提供的证据表明，人血浆中存在的apo（a）片段是人尿液中apo（a）片段的来源。如果是这种情况，预计终末期肾病（ESRD）受试者的血浆片段水平会更高。在本文中，我们定量了26名白人和26名非洲裔美国人ESRD受试者以及52名种族、性别和apo（a）亚型大小匹配的健康受试者的apo（a）片段和血浆Lp（a）水平。终末期肾病患者血浆载脂蛋白（a）片段和脂蛋白（a）水平均较高。此外，在ESRD中，载脂蛋白（a）片段与总免疫可检测载脂蛋白（a）的比率增加。为了确定apo（a）片段的增加对ESRD中血浆Lp（a）增加的贡献程度，采用两种不同的抗apo（a）酶联免疫吸附试验（ELISA）测量血浆Lp（a）水平。一种试验检测游离和结合载脂蛋白（a），而另一种试验仅检测结合载脂蛋白（a）。尽管使用检测片段和全长apo（a）的测定法，ESRD受试者的apo（a）血浆水平往往较高，但增加幅度不大。因此，尽管ESRD血浆中大部分载脂蛋白（a）以碎片形式循环，但与肾功能不全相关的血浆Lp（a）水平升高的大部分原因是完整Lp（a）增加。
Apolipoprotein(a) [apo(a)] is a plasma glycoprotein that is highly polymorphic in size due to differences in the number of a tandemly arrayed cysteine‐rich repeat called kringle (K)4 at its N‐terminus. Most plasma apo(a) is covalently attached to apolipoprotein B‐100 and circulates as part of lipoprotein(a) [Lp(a)]. A fraction of apo(a) circulates free of lipoproteins. Almost all of the free apo(a) consists of fragments containing variable numbers of K4 repeats derived from the N‐terminal region. Previously we provided evidence suggesting that the apo(a) fragments present in human plasma are the source of the apo(a) fragments in human urine. If this were the case, it would be expected that plasma levels of fragments would be higher in subjects with end‐stage renal disease (ESRD). In this paper we quantified the levels of apo(a) fragments and plasma Lp(a) in 26 Caucasian and 26 African‐American subjects with ESRD and 52 healthy subjects matched for race, sex and the size of the apo(a) isoforms. The plasma levels of apo(a) fragments and Lp(a) were both higher in the ESRD subjects. In addition, the ratio of apo (a) fragments to total immunodetectable apo(a) was increased in ESRD. To determine how much the increase in the apo(a) fragments contributed to the increase in plasma Lp(a) in ESRD, the plasma Lp(a) levels were measured employing two different anti‐apo(a) enzyme‐linked immunoabsorption assays (ELISA). One assay detected both free and bound apo(a), whereas the other assay detected only bound apo(a). Although the plasma levels of apo(a) in the ESRD subjects tended to be higher using the assay that detected both fragments and full‐length apo(a), the increase was modest. Thus, although a greater proportion of the apo(a) in ESRD plasma circulates as fragments, most of the elevation in plasma levels of Lp(a) associated with renal insufficiency is due to an increase in intact Lp(a).