Saku K, Gartside P S, Hynd B A, Mendoza S G, Kashyap M L
Metabolism. 1985 Aug;34(8):754-64. doi: 10.1016/0026-0495(85)90027-7.
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. Autologous 125I labeled HDL were injected intravenously (IV; 25 microCi) 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 less than 0.001) in patients than normals (70.4 +/- 2.7 v 106.9 +/- 7.0; 24.2 +/- 1.6 v 39.2 +/- 0.9 mg/dL, respectively). The mean fractional catabolic rates (FCR) obtained from plasma 125I-HDL, apo AI, apo AII radioactivity decay curves and by Berson and Yalow's method (urine/plasma radioactivity ratios) were significantly greater (P less than 0.05) in patients than in controls (0.387 v 0.299; 0.391 v 0.309; 0.361 v 0.275; 0.272 v 0.207/d; respectively). The mean synthetic rates (SR) of apo AI and apo AII were significantly lower in patients than in controls (11.12 v 14.17 mg/kg body weight/d, P less than 0.05; 3.53 v 4.68 mg/kg body weight/d, P less than 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.
在大多数家族性高甘油三酯血症患者中，血浆高密度脂蛋白（HDL）及其主要蛋白质——载脂蛋白（apo）AI和apo AII——水平低于正常。然而，血浆apo AI和apo AII水平降低的病理生理学尚不清楚。对6例患有与家族性高甘油三酯血症相关的原发性HDL缺乏症的瘦患者和5例血脂正常的对照者进行了HDL apo AI和apo AII的动力学参数（周转率）研究。静脉注射（IV；25微居里）自体125I标记的HDL，注射后10分钟采集血样，此后每隔一定时间采集血样，共采集12天。每天收集尿样并测量其放射性。使用三个指数从衰变曲线下的面积计算动力学参数。患者的平均血浆apo AI和apo AII水平显著低于正常人（P<0.001）（分别为70.4±2.7对106.9±7.0；24.2±1.6对39.2±0.9毫克/分升）。从血浆125I-HDL、apo AI、apo AII放射性衰变曲线以及通过Berson和Yalow方法（尿/血浆放射性比值）获得的平均分数分解代谢率（FCR）在患者中显著高于对照组（P<0.05）（分别为0.387对0.299；0.391对0.309；0.361对0.275；0.272对0.207/天）。患者中apo AI和apo AII的平均合成率（SR）显著低于对照组（分别为11.12对14.17毫克/千克体重/天，P<0.05；3.53对4.68毫克/千克体重/天，P<0.05）。用牛脂蛋白脂肪酶对富含甘油三酯（TG）的脂蛋白进行体外脂解，并测量肝素后血浆中的肝TG脂肪酶和脂蛋白脂肪酶，患者和对照组的结果相似，表明与HDL和TG分解代谢相关的这些因素没有异常。然而，发现肝TG脂肪酶与apo AI和apo AII的FCR之间存在显著正相关。数据表明，在这一系列HDL缺乏症患者中，血浆HDL胆固醇、apo AI和apo AII水平降低是由于apo AI和apo AII（HDL的主要蛋白质）合成减少以及分数分解代谢率增加所致。
