Mooser V, Marcovina S M, Wang J, Hobbs H H
Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Clin Genet. 1997 Nov;52(5):387-92. doi: 10.1111/j.1399-0004.1997.tb04358.x.
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).
载脂蛋白(a)[apo(a)]是一种血浆糖蛋白，由于其N端串联排列的富含半胱氨酸重复序列（称为kringle [K]4）数量不同，其大小具有高度多态性。大多数血浆apo(a)与载脂蛋白B-100共价结合，并作为脂蛋白(a)[Lp(a)]的一部分循环。一部分apo(a)以游离脂蛋白的形式循环。几乎所有游离的apo(a)都由包含可变数量源自N端区域的K4重复序列的片段组成。此前我们提供的证据表明，人血浆中存在的apo(a)片段是人尿中apo(a)片段的来源。如果是这样的话，预计终末期肾病（ESRD）患者血浆中片段水平会更高。在本文中，我们对26名白种人和26名非裔美国ESRD患者以及52名种族、性别和apo(a)异构体大小匹配的健康受试者的apo(a)片段和血浆Lp(a)水平进行了定量。ESRD患者的血浆apo(a)片段和Lp(a)水平均较高。此外，ESRD患者中apo(a)片段与总免疫可检测apo(a)的比率增加。为了确定apo(a)片段的增加对ESRD患者血浆Lp(a)增加的贡献程度，我们采用两种不同的抗apo(a)酶联免疫吸附测定（ELISA）来测量血浆Lp(a)水平。一种测定法可检测游离和结合的apo(a)，而另一种测定法仅检测结合的apo(a)。尽管使用能同时检测片段和全长apo(a)的测定法时，ESRD患者的血浆apo(a)水平往往更高，但升高幅度不大。因此，尽管ESRD血浆中更大比例的apo(a)以片段形式循环，但与肾功能不全相关的血浆Lp(a)水平升高主要是由于完整Lp(a)的增加。
