The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit
The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit
复制标题
DOI：
10.1016/j.freeradbiomed.2005.01.008
复制
发表时间：
2005-05-01
影响因子：
7.4
通讯作者：
Halliwell, B
中科院分区：
文献类型：
--
作者：
Ren, MQ;Rajendran, R;Halliwell, B
一些流行病学研究表明，铁储备的增加与动脉粥样硬化事件的增加有关。为了验证降低血管中铁水平会减缓病变生长的假说，我们研究了铁络合剂Desferal(72 mg/kg/天，5天/周)对胆固醇喂养的新西兰大白兔动脉粥样硬化和病变铁含量的影响。用1%w/w胆固醇饲料喂养8周(最后5周每日注射地塞米松)或12周(最后9周注射地塞米松)。对照组注射生理盐水。与12周对照组相比，治疗12周的动物的平均病变面积显著减少(p=0.038)。使用核显微镜结合扫描透射式离子显微镜、卢瑟福背散射光谱和粒子诱导的X射线发射，12周治疗组动物(58ppm干重量)的平均病变铁水平也显著低于12周对照组动物(95ppm干重量)(p=0.030)。与对照组相比，治疗8周的动物没有观察到病变面积或铁含量的减少，也没有观察到两组病变锌浓度的变化。我们的数据强化了铁在动脉粥样硬化发展的早期阶段起作用的概念。(C)2005 Elsevier Inc.保留所有权利。
Several epidemiological studies have suggested that increased iron stores are associated with increased atherosclerotic events. In order to test the hypothesis that decreasing the vascular level of iron slows lesion growth, we examined the effects of the iron chelator Desferal (72 mg/kg/day, 5 days/week) on atherosclerosis and lesion iron content in cholesterol-fed New Zealand White rabbits. Rabbits were fed with a 1% w/w cholesterol diet for either 8 weeks (and for the last 5 weeks injected daily with Desferal) or 12 weeks (and for the last 9 weeks injected with Desferal). Controls were injected with saline. A significant reduction in average lesion area (p = 0.038) was observed in the 12-week treated animals compared with the 12-week controls. The average lesion iron level of the 12-week treated animals (58 ppm dry wt) was also significantly lower (p = 0.030) than in 12-week control animals (95 ppm dry wt), as measured using nuclear microscopy with the combination of scanning transmission ion microscopy, Rutherford back-scattering spectroscopy, and particle-induced X-ray emission. No reduction in lesion area or iron content was observed in the 8-week treated animals compared with controls, and no change in lesion zinc concentration was observed for either group. Our data strengthen the concept that iron contributes to the early stages of the development of atherosclerosis. (c) 2005 Elsevier Inc. All rights reserved.