Knight B L, Perombelon Y F, Soutar A K, Wade D P, Seed M
MRC Lipoprotein Team, Hammersmith Hospital, London, U.K.
Atherosclerosis. 1991 Apr;87(2-3):227-37. doi: 10.1016/0021-9150(91)90025-x.
The in vivo turnover of autologous lipoprotein(a) (Lp(a)) was studied in four heterozygous familial hypercholesterolaemic (FH) subjects and four subjects who were hyperlipidaemic but not FH. Each of the FH subjects exhibited a much lower fractional catabolic rate (FCR) for LDL than each of the non-FH subjects. Lp(a) was purified by sequential density gradient centrifugations and was radio-iodinated. The labelled Lp(a) ran as a single band on electrophoresis in gradient polyacrylamide gels. Less than 5% of the label was in lipid, with about 40% of the remainder on apolipoprotein B (apo B) and 60% on apo(a). Labelled and unlabelled Lp(a) competed equally poorly with LDL for binding to LDL receptors on cultured fibroblasts. The FCR of Lp(a), calculated from the decay of the specific radioactivity of the Lp(a) isolated from the daily blood samples, was the same in FH subjects as in non-FH subjects. There was no consistent relationship between Lp(a) FCR and the plasma Lp(a) concentration or between FCR and the Lp(a) phenotype, at least within this sample of subjects. There was a strong association between Lp(a) concentration and production rate, with values for non-FH and FH subjects falling on the same line. The rate of decline of radioactivity in whole plasma was consistently slower than the fall in specific radioactivity of the isolated Lp(a). This difference was more marked in FH subjects than in non-FH subjects and resulted from the accumulation of radioactivity derived from the injected Lp(a) at a lower density than Lp(a), in the fractions containing LDL. The amount of radioactivity in this fraction increased for the first few days after injection and then fell, the fall being more rapid in non-FH than in FH subjects. These results provide no evidence for the involvement of LDL receptors in the catabolism of Lp(a) itself but suggest that they could be responsible for some of the clearance of the lipid and apo B components after removal of apo(a) in the circulation.
在四名杂合子家族性高胆固醇血症（FH）患者和四名血脂异常但非FH的受试者中研究了自体脂蛋白（a）[Lp（a）]的体内周转率。与每名非FH受试者相比，每名FH受试者的低密度脂蛋白（LDL）分数分解代谢率（FCR）均低得多。通过连续密度梯度离心法纯化Lp（a）并进行放射性碘化。标记的Lp（a）在梯度聚丙烯酰胺凝胶电泳中呈单一条带。少于5%的标记物存在于脂质中，其余约40%在载脂蛋白B（apo B）上，60%在载脂蛋白（a）[apo（a）]上。标记的和未标记的Lp（a）与LDL竞争结合培养成纤维细胞上的LDL受体的能力同样差。根据从每日血样中分离的Lp（a）的比放射性衰减计算得出的Lp（a）的FCR在FH受试者和非FH受试者中相同。至少在该受试者样本中，Lp（a）FCR与血浆Lp（a）浓度之间或FCR与Lp（a）表型之间没有一致的关系。Lp（a）浓度与生成率之间存在很强的关联，非FH和FH受试者的值落在同一条线上。全血中放射性的下降速率始终比分离的Lp（a）的比放射性下降慢。这种差异在FH受试者中比在非FH受试者中更明显，是由于注射的Lp（a）衍生的放射性在低密度脂蛋白（LDL）所在的组分中积累，其密度低于Lp（a）。该组分中的放射性量在注射后的头几天增加，然后下降，非FH受试者的下降比FH受试者更快。这些结果没有提供LDL受体参与Lp（a）自身分解代谢的证据，但表明它们可能负责循环中apo（a）去除后脂质和apo B成分的部分清除。
