Angioplasty-induced superoxide anions and neointimal hyperplasia in the rabbit carotid artery: suppression by the isoflavone trans-tetrahydrodaidzein.

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 antiproliferative actions of trans-THD in injured arteries. Strategies using such isoflavones may be useful for preventing restenosis after vascular manipulations in humans.