Rader D J, Mann W A, Cain W, Kraft H G, Usher D, Zech L A, Hoeg J M, Davignon J, Lupien P, Grossman M
Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
J Clin Invest. 1995 Mar;95(3):1403-8. doi: 10.1172/JCI117794.
Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL). The role of the LDL receptor in the catabolism of Lp(a) has been controversial. We therefore investigated the in vivo catabolism of Lp(a) and LDL in five unrelated patients with homozygous familial hypercholesterolemia (FH) who have little or no LDL receptor activity. Purified 125I-Lp(a) and 131I-LDL were simultaneously injected into the homozygous FH patients, their heterozygous FH parents when available, and control subjects. The disappearance of plasma radioactivity was followed over time. As expected, the fractional catabolic rates (FCR) of 131I-LDL were markedly decreased in the homozygous FH patients (mean LDL FCR 0.190 d-1) and somewhat decreased in the heterozygous FH parents (mean LDL FCR 0.294 d-1) compared with controls (mean LDL FCR 0.401 d-1). In contrast, the catabolism of 125I-Lp(a) was not significantly different in the homozygous FH patients (mean FCR 0.251 d-1), heterozygous FH parents (mean FCR 0.254 d-1), and control subjects (mean FCR 0.287 d-1). In summary, absence of a functional LDL receptor does not result in delayed catabolism of Lp(a), indicating that the LDL receptor is not a physiologically important route of Lp(a) catabolism in humans.
脂蛋白(a)[Lp(a)]是一种致动脉粥样硬化脂蛋白，其结构与低密度脂蛋白(LDL)相似。LDL受体在Lp(a)分解代谢中的作用一直存在争议。因此，我们研究了5例无亲缘关系的纯合子家族性高胆固醇血症(FH)患者体内Lp(a)和LDL的分解代谢情况，这些患者几乎没有或没有LDL受体活性。将纯化的125I-Lp(a)和131I-LDL同时注射到纯合子FH患者、如有则注射到其杂合子FH父母以及对照受试者体内。随着时间的推移跟踪血浆放射性的消失情况。正如预期的那样，与对照组(平均LDL FCR 0.401 d-1)相比，纯合子FH患者中131I-LDL的分解代谢率(FCR)显著降低(平均LDL FCR 0.190 d-1)，杂合子FH父母中的分解代谢率有所降低(平均LDL FCR 0.294 d-1)。相比之下，125I-Lp(a)在纯合子FH患者(平均FCR 0.251 d-1)、杂合子FH父母(平均FCR 0.254 d-1)和对照受试者(平均FCR 0.287 d-1)中的分解代谢没有显著差异。总之，缺乏功能性LDL受体不会导致Lp(a)分解代谢延迟，这表明LDL受体在人类Lp(a)分解代谢中不是生理上重要的途径。
