Apolipoprotein AI and AII metabolism in patients with primary high-density lipoprotein deficiency associated with familial hypertriglyceridemia.
Apolipoprotein AI and AII metabolism in patients with primary high-density lipoprotein deficiency associated with familial hypertriglyceridemia.
复制标题
与家族性高甘油三酯血症相关的原发性高密度脂蛋白缺乏症患者的载脂蛋白 AI 和 AII 代谢。
DOI：
10.1016/0026-0495(85)90027-7
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Kashyap,ML
中科院分区：
文献类型：
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作者：
Saku,K;Gartside,PS;Hynd,BA;Mendoza,SG;Kashyap,ML
大多数家族性高脂血症患者的血浆高密度脂蛋白（HDL）及其主要蛋白载脂蛋白（apo）AI和apo AII低于正常值。然而，低血浆载脂蛋白AI和载脂蛋白AII的病理生理学尚不清楚。对6例原发性HDL缺乏症伴家族性高脂血症的瘦型患者和5例正常血脂对照者的HDL、apo AI和apo AII的动力学参数（周转率）进行了研究。静脉注射自体125I标记的HDL（IV; 25 μ Ci），并在注射后10分钟抽取血样，此后定期抽取血样，持续12天。每天采集尿样并测量其放射性。使用三个指数从衰减曲线下的面积计算动力学参数。血浆apo AI和apo AII水平分别为70.4 ± 2.7v106.9 ± 7.0; 24.2 ± 1.6v39.2 ± 0.9 mg/dL，均显著低于正常人（P <0.001）。由血浆~（125）I-HDL、apo AI、apo AII放射性衰变曲线及贝尔森和Yalow法（尿/血浆放射性比值）计算的平均分解率（FCR），患者组均显著高于对照组（P <0.05）（分别为0.387 v0.299; 0.391 v0.309; 0.361 v0.275; 0.272 v0.207/d）。载脂蛋白AI和载脂蛋白AII的平均合成率（SR）在患者组明显低于对照组（分别为11.12v14.17mg/kg体重/d，P <0.05; 3.53v4.68mg/kg体重/d，P <0.05）。在体外，牛脂蛋白脂肪酶对富含甘油三酯（TG）的脂蛋白的脂解，以及肝素后血浆中肝TG脂肪酶和脂蛋白脂肪酶的测量结果在患者和对照组中相似，表明这些与HDL和TG催化剂相关的因子无异常。结果表明，HDL缺乏症患者血浆HDL-胆固醇、载脂蛋白AI和载脂蛋白AII水平的降低是由于HDL的主要蛋白apo AI和apo AII的合成减少和分解率增加所致。
Plasma high-density lipoproteins (HDL) and their major proteins—apolipoprotein (apo) AI and apo AII—are subnormal in most patients with familial hypertriglyceridemia. However, the pathophysiology of low-plasma apo AI and apo AII is unclear. The kinetic parameters (turnover) of HDL apo AI and apo AII were studied in six lean patients with primary HDL deficiency associated with familial hypertriglyceridemia and five normolipidemic controls. Autologous125I labeled HDL were injected intravenously (IV; 25 μCi) and blood samples drawn ten minutes after the injection and periodically thereafter for 12 days. Urine samples were collected daily and their radioactivity measured. Kinetic parameters were calculated from the area under the decay curve using three exponentials. Mean plasma apo AI and apo AII were significantly lower (P< 0.001) in patients than normals (70.4 ± 2.7v106.9 ± 7.0; 24.2 ± 1.6v39.2 ± 0.9 mg/dL, respectively). The mean fractional catabolic rates (FCR) obtained from plasma125I-HDL, apo AI, apo AII radioactivity decay curves and by Berson and Yalow's method (urine/plasma radioactivity ratios) were significantly greater (P< 0.05) in patients than in controls (0.387v0.299; 0.391v0.309; 0.361v0.275; 0.272v0.207/d; respectively). The mean synthetic rates (SR) of apo AI and apo AII were significantly lower in patients than in controls (11.12v14.17 mg/kg body weight/d,P< 0.05; 3.53v4.68 mg/kg body weight/d,P< 0.05, respectively). In vitro lipolysis of triglyceride (TG) rich lipoproteins by bovine lipoprotein lipase, and measurement of hepatic TG lipase and lipoprotein lipase in postheparin plasma were similar in patients and controls, indicating no abnormality in these factors that are linked to HDL and TG catabolism. However, a significant positive correlation between hepatic TG lipase and the FCR of apo AI and apo AII was found. The data suggest that in this series of patients with HDL deficiency the low plasma HDL-cholesterol, apo AI, and apo AII levels resulted from decreased synthesis and an increased fractional catabolic rate of apo AI and apo AII, the major proteins of HDL.