Pirich C, Sinzinger H
Department of Nuclear Medicine, University of Vienna, Austria.
Ann N Y Acad Sci. 1995 Jan 17;748:613-21. doi: 10.1111/j.1749-6632.1994.tb17374.x.
Radiolabeling of autologous LDL allows in vivo characterization of arterial wall lipid metabolism and LDL receptor imaging. Different kinetic types of arterial wall LDL entry reflect the de-, re-, and endothelialized segments in both animals and humans. In 36 male cholesterol-fed rabbits being treated with the calcium channel blocker isradipine (0.3 mg/kg daily), the retention of the radiolabeled (125I-LDL) was reduced, being related to the reduction in arterial wall cholesterol ester content and the decreased extent of Sudan III-positive areas. In parallel, a significant (p < 0.01) increase in vascular prostaglandin I2 (PGI2) generation was seen in endothelialized and reendothelialized segments of the abdominal aorta. These effects were completely abolished by concomitant treatment with acetylicsalicylic acid (ASA). These data could be confirmed in humans, too: a 4-week treatment with prostaglandin E1 (PGE1:5 ng/kg/min iv, 5 days/week, 6 h/day for 6 weeks) and isradipine (2 x 2.5 mg po daily for 4 weeks) did not change arterial 123I-LDL influx kinetics, which were examined over a total of 60 (PGE1) and 96 (isradipine) vascular regions. In contrast to this, the retention of the tracer was significantly diminished in different arterial segments. In isradipine-treated patients, 20 hours after reinjection of radiolabeled LDL, the quantitative LDL entry was reduced by at least 4.7% with a maximum of 23.5% (p < 0.01) in type I (n = 50 lesions) or type II lesions (n = 41). PGE1 treatment induced a 16.9% to 30.7% (p < 0.01) decrease of LDL retention in type I (n = 36 lesions) or type II lesions (n = 24), respectively. These findings support the hypothesis derived from earlier experimental studies that the antiatherosclerotic effects are likely to be due to the increase in PGE1 and/or PGI2 availability mediated by an increase in cAMP. The results demonstrate the potential of 123I-LDL scintigraphy for the characterization of vascular LDL kinetics and the monitoring of functional lipid lesion regression.
对自体低密度脂蛋白（LDL）进行放射性标记可在体内对动脉壁脂质代谢和LDL受体成像进行表征。不同动力学类型的动脉壁LDL进入反映了动物和人类动脉壁的脱内皮、再内皮化和内皮化节段。在36只接受钙通道阻滞剂伊拉地平（每日0.3 mg/kg）治疗的雄性高胆固醇喂养兔中，放射性标记物（125I-LDL）的滞留减少，这与动脉壁胆固醇酯含量的降低以及苏丹III阳性区域范围的减小有关。同时，在腹主动脉的内皮化和再内皮化节段中，血管前列腺素I2（PGI2）生成显著增加（p < 0.01）。乙酰水杨酸（ASA）联合治疗可完全消除这些作用。这些数据在人体中也得到了证实：用前列腺素E1（PGE1：5 ng/kg/min静脉注射，每周5天，每天6小时，共6周）和伊拉地平（每日口服2×2.5 mg，共4周）进行4周治疗后，未改变动脉123I-LDL流入动力学，共检查了60个（PGE1组）和96个（伊拉地平组）血管区域。与此相反，示踪剂在不同动脉节段的滞留显著减少。在伊拉地平治疗的患者中，再次注射放射性标记LDL后20小时，I型（n = 50个病变）或II型病变（n = 41个）中定量LDL进入至少减少4.7%，最大减少23.5%（p < 0.01）。PGE1治疗分别使I型（n = 36个病变）或II型病变（n = 24个）中LDL滞留减少16.9%至30.7%（p < 0.01）。这些发现支持了早期实验研究得出的假设，即抗动脉粥样硬化作用可能是由于cAMP增加介导的PGE1和/或PGI2可用性增加所致。结果表明123I-LDL闪烁显像在表征血管LDL动力学和监测功能性脂质病变消退方面具有潜力。
