Angioplasty-induced superoxide anions and neointimal hyperplasia in the rabbit carotid artery:: suppression by the isoflavone trans-tetrahydrodaidzein
Angioplasty-induced superoxide anions and neointimal hyperplasia in the rabbit carotid artery:: suppression by the isoflavone trans-tetrahydrodaidzein
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DOI：
10.1016/j.atherosclerosis.2004.05.003
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发表时间：
2004-09-01
期刊：
影响因子：
5.3
通讯作者：
Bobik, A
中科院分区：
文献类型：
--
作者：
Kanellakis, P;Nestel, P;Bobik, A
活性氧（ROS）可能有助于球囊导管损伤动脉狭窄的发展。由于葛根素酮在体外对ROS和细胞增殖表现出作用，似乎可用于预防这种狭窄，我们研究了葛根素反式-四氢大豆苷元（trans-THD）对球囊导管损伤动脉中ROS升高相关的新生内膜病变发展的影响。用膨胀的球囊导管损伤用载体或trans-THD处理的兔的颈动脉，并在随后的28天内测定细胞增殖、胶原含量、ROS和血管结构。损伤后7天，新生内膜平滑肌细胞增殖减少了50%（p < 0.05），而中膜细胞增殖基本上未受影响（p > 0.10）。此时，与未损伤的动脉相比，载体处理的兔中的ROS水平升高3倍（p < 0.05）。用trans-THD治疗使ROS水平降低至未损伤动脉中所见的水平（p > 0.05）。trans-THD对内膜细胞增殖的抗增殖作用在损伤后14天持续存在，并且在损伤后28天，trans-THD治疗的动物的管腔尺寸增加了27%（p < 0.05），内膜面积：血管面积减少了40%（p < 0.05）。trans-THD对胶原蛋白蓄积的微小影响无统计学显著性，表明对新生内膜细胞增殖的影响是该药物减弱新生内膜发育的主要机制。内膜平滑肌细胞和ROS是trans-THD在损伤动脉中抗增殖作用的潜在重要靶点。使用这种二氢黄酮的策略可能有助于预防人类血管操作后的再狭窄。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Reactive oxygen species (ROS) may contribute to the development of stenosis in balloon catheter injured arteries. As isoflavones exhibit effects on ROS and cell proliferation In vitro that appear useful in preventing such stenosis, we examined the effects of the isoflavone trans-tetrahydrodaidzein (trans-THD) on development of neointimal lesions in relation to elevations in ROS in balloon catheter injured arteries. Carotid arteries of rabbits treated with either vehicle or trans-THD were injured with an inflated balloon catheter and cell proliferation, collagen content, ROS and vessel structure determined over the ensuing 28 days. Seven days after injury neointimal smooth muscle cell proliferation was reduced by 50% (p < 0.05) whilst medial cell proliferation was largely unaffected (p > 0.10). At this time ROS levels in vehicle-treated rabbits were elevated 3-fold compared to uninjured arteries (p < 0.05). Treatment with trans-THD reduced ROS levels to those seen in uninjured arteries (p > 0.05). The antiproliferative effects of trans-THD on intimal cell proliferation persisted 14 days after the injury, and twenty eight days after injury the size of the lumen in trans-THD-treated animals was 27% greater (p < 0.05) and the intima area: vessel area reduced by 40% (p < 0.05). The small effects of trans-THD on collagen accumulation was not statistically significant, indicating that effects on neointimal cell proliferation was the major mechanism by which this isoflavone attenuated development of the neointima. Intimal smooth muscle cells and ROS represent potentially important targets for the anti proliferative actions of trans-THD in injured arteries. Strategies using such isoflavones may be useful for preventing restenosis after vascular manipulations in humans. (C) 2004 Elsevier Ireland Ltd. All rights reserved.