Tilly-Kiesi M, Packard C J, Kahri J, Ehnholm C, Shepherd J, Taskinen M R
Department of Medicine, Helsinki University Central Hospital, Finland.
Atherosclerosis. 1997 Feb 10;128(2):213-22. doi: 10.1016/s0021-9150(96)05992-8.
Apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) represent 80 90% of the protein content of high density lipoproteins (HDL). Previously we have identified a Finnish family with an apo A-I variant (Lys107-->0) associated with reduced plasma HDL cholesterol level and decreased lipoprotein (Lp)(AI w AII) concentration compared to unaffected family members. To determine the in vivo metabolism of apo A-I and apo A-II in the carriers of apo A-I (Lys107-->0) variant we radioiodinated normal apo A-I with 125I and apo A-II with 131I and compared the kinetic data of two heterozygous apo A-I(Lysl07-->0) patients (HDL cholesterol leves 0.31 and 0.69 mmol/l) to that of eight normolipidemic, healthy control subjects. Plasma radioactivity curves of 125I-labelled normal apo A-I of the patients demonstrated accelerated clearance of apo A-I compared to control subjects. In the two patients the fractional catabolic rates (FCR) of apo A-I were 0.347/day and 0.213/day, respectively, while the mean FCR of apo A-I of the control subjects was 0.151 +/- 0.041/day. Similarly, the plasma decay curves of the 131I-labelled apo A-II showed more rapid clearance of apo A-II in the two patients than in control subjects. The FCR of apo A-II in the two patients were 0.470/day and 0.234/day, while the mean FCR of apo A-II in control subjects was 0.154 +/- 0.029/day. The calculated production rates of apo A-I were similar in patients and in control subjects, and the production rates of apo A-II were significantly higher in patients than in control subjects. Our results show that the Lp(AI w AII) deficiency in patients with the apo A-I(Lys107-->0) is associated with increased fractional catabolic rates of normal apo A-I and apo A-II, while the production rates of these apolipoproteins are normal (apo A-I) or slightly increased (apo A-II).
载脂蛋白A-I（apo A-I）和载脂蛋白A-II（apo A-II）占高密度脂蛋白（HDL）蛋白质含量的80%至90%。此前我们鉴定出一个芬兰家族，其apo A-I存在一种变体（Lys107→0），与未受影响的家族成员相比，该变体与血浆HDL胆固醇水平降低以及脂蛋白（Lp）（AI与AII）浓度下降有关。为了确定apo A-I（Lys107→0）变体携带者体内apo A-I和apo A-II的代谢情况，我们用125I对正常apo A-I进行放射性碘化，用131I对apo A-II进行放射性碘化，并将两名杂合apo A-I（Lys107→0）患者（HDL胆固醇水平分别为0.31和0.69 mmol/l）的动力学数据与八名血脂正常的健康对照者的数据进行比较。患者125I标记的正常apo A-I的血浆放射性曲线显示，与对照者相比，apo A-I的清除加速。在这两名患者中，apo A-I的分解代谢率（FCR）分别为0.347/天和0.213/天，而对照者apo A-I的平均FCR为0.151±0.041/天。同样，131I标记的apo A-II的血浆衰变曲线显示，这两名患者中apo A-II的清除比对照者更快。这两名患者中apo A-II的FCR分别为0.470/天和0.234/天，而对照者中apo A-II的平均FCR为0.154±0.029/天。患者和对照者中apo A-I的计算生成率相似，患者中apo A-II的生成率显著高于对照者。我们的结果表明，apo A-I（Lys107→0）患者的Lp（AI与AII）缺乏与正常apo A-I和apo A-II的分解代谢率增加有关，而这些载脂蛋白的生成率正常（apo A-I）或略有增加（apo A-II）。
