In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients
In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients
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DOI：
10.1038/sj.ki.5002131
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发表时间：
2007-05-01
影响因子：
19.6
通讯作者：
Dieplinger, H.
中科院分区：
文献类型：
--
作者：
Frischmann, M. E.;Kronenberg, F.;Dieplinger, H.
脂蛋白（a）（Lp（a））由低密度脂蛋白样颗粒和共价连接的高度糖基化的蛋白质组成，称为载脂蛋白（a）（apo（a））。脂蛋白（a）来源于肝脏，但其催化剂仍然知之甚少。血液透析（HD）患者中这种高度致动脉粥样硬化的脂蛋白的血浆浓度升高，表明肾脏参与Lp（a）的代谢。因此，我们比较了通过稳定同位素技术在7名HD患者和9名健康对照中测定的Lp（a）的两种蛋白组分（即apo（a）和apoB）的体内转换率。血液透析患者Lp（a）-apo（a）的分解率（FCR）显著低于对照组（0.164 +/- 0.114 vs 0.246 +/- 0.067天（-1），P = 0.042）。Lp（a）-apoB的FCR也是如此（0.129 +/- 0.097 vs 0.299 +/- 0.142天（-1），P = 0.005）。这导致HD患者中Lp（a）-apo（a）和Lp（a）-apoB的滞留时间分别为8.9天和12.9天，远长于对照组（分别为4.4天和3.9天）。Lp（a）产生apo（a）和apoB的速率在患者和对照组之间没有显著差异，当与具有相似Lp（a）血浆浓度的对照组相比时，患者的apo（a）和apoB的产生速率甚至更低。这项体内转换研究是了解Lp（a）催化剂机制的进一步关键步骤：HD患者肾功能丧失导致Lp（a）血浆水平升高，因为清除率降低，但Lp（a）的产生并未增加。血液透析患者Lp（a）的滞留时间延长可能是其动脉粥样硬化风险增高的重要原因。
Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein-like particle and a covalently linked highly glycosylated protein, called apolipoprotein(a) (apo(a)). Lp(a) derives from the liver but its catabolism is still poorly understood. Plasma concentrations of this highly atherogenic lipoprotein are elevated in hemodialysis (HD) patients, suggesting the kidney to be involved in Lp(a) catabolism. We therefore compared the in vivo turnover rates of both protein components from Lp(a) (i.e. apo(a) and apoB) determined by stable- isotope technology in seven HD patients with those of nine healthy controls. The fractional catabolic rate (FCR) of Lp(a)-apo(a) was significantly lower in HD patients compared with controls (0.164 +/- 0.114 vs 0.246 +/- 0.067 days(-1), P = 0.042). The same was true for the FCR of Lp(a)-apoB ( 0.129 +/- 0.097 vs 0.299 +/- 0.142 days(-1), P = 0.005). This resulted in a much longer residence time of 8.9 days for Lp(a)-apo(a) and 12.9 days for Lp(a)-apoB in HD patients compared with controls (4.4 and 3.9 days, respectively). The production rates of apo(a) and apoB from Lp(a) did not differ significantly between patients and controls and were even lower for patients when compared with controls with similar Lp(a) plasma concentrations. This in vivo turnover study is a further crucial step in understanding the mechanism of Lp(a) catabolism: the loss of renal function in HD patients causes elevated Lp(a) plasma levels because of decreased clearance but not increased production of Lp(a). The prolonged retention time of Lp(a) in HD patients might importantly contribute to the high risk of atherosclerosis in these patients.