Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.
Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.
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含有 Kringle 的载脂蛋白 (a) 片段在人血浆中循环并排泄到尿液中。
DOI：
10.1172/jci119055
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Hobbs,HH
中科院分区：
文献类型：
--
作者：
Mooser,V;Marcovina,SM;White,AL;Hobbs,HH
载脂蛋白(a) [apo(a)]含有多个kringle 4重复序列，并作为脂蛋白(a) [Lp(a)]的一部分循环。载脂蛋白(a)由肝脏合成，但其清除机制尚不清楚。先前，我们发现人类尿液中存在含kringle 4的载脂蛋白(a)片段。为了探究它们的来源，我们检查了人血浆，发现了一系列比尿碎片大的载脂蛋白(a)免疫反应肽。血浆载脂蛋白(a)片段浓度与血浆Lp(a)水平及24h尿载脂蛋白(a)排泄量有直接关系。血浆Lp(a)水平低（< 2 mg/dl）的个体在血浆中以碎片形式循环的载脂蛋白(a)比例较高。在狒狒血浆中发现了类似的载脂蛋白(a)片段，但在狒狒肝细胞原代培养的条件培养基中没有发现，这表明载脂蛋白(a)片段是由循环载脂蛋白(a)或脂蛋白(a)产生的。当从人血浆中纯化的载脂蛋白(a)片段静脉注射到不产生载脂蛋白(a)的小鼠体内时，在小鼠尿液中很容易检测到与人类尿液中发现的相似的载脂蛋白(a)片段。因此，我们认为人血浆中的载脂蛋白(a)片段来源于循环载脂蛋白(a)/脂蛋白(a)，并且是尿载脂蛋白(a)的来源。
Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly related to the plasma level of Lp(a) and the 24-h urinary excretion of apo(a). Individuals with low (< 2 mg/dl) plasma levels of Lp(a) had proportionally more apo(a) circulating as fragments in their plasma. Similar apo(a) fragments were identified in baboon plasma but not in conditioned media from primary cultures of baboon hepatocytes, suggesting that the apo(a) fragments are generated from circulating apo(a) or Lp(a). When apo(a) fragments purified from human plasma were injected intravenously into mice, a species that does not produce apo(a), apo(a) fragments similar to those found in human urine were readily detected in mouse urine. Thus, we propose that apo(a) fragments in human plasma are derived from circulating apo(a)/Lp(a) and are the source of urinary apo(a).