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Ribonucleotide Reductase Inhibitors Reduce Atherosclerosis in a Double-Injury Rabbit Model.

机译:核糖核苷酸还原酶抑制剂可减轻兔双损伤模型的动脉粥样硬化。

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Atheroproliferative disorders such as atherosclerosis are an important health problem and one of the leading causes of morbidity and mortality in the United States. Minimally invasive therapeutic procedures, including angioplasty with stent deployment, are used frequently for obstructive coronary artery disease. However, restenosis, a proliferative vascular response, is a common sequela to this procedure. The current study investigated the effect of inhibiting ribonucleotide reductase (RR), an enzyme necessary for cellular proliferation, in an attempt to ameliorate the proliferative response. Two RR inhibitors, didox and hydroxyurea, were chosen for their potent antiproliferative properties. Studies were carried out by using a double-injury rabbit model, in which endothelial denudation was followed by the administration of a high-fat diet. At 4 wk after initial endothelial denudation, the developing atherosclerotic lesion was subjected to transluminal balloon dilation to simulate clinical intervention with percutaneous transluminal angioplasty. The degree of restenosis and atheroproliferation was assessed at 8 wk. Histologic evaluation of the lesion demonstrated that treatment with didox and hydroxyurea significantly decreased lesion area and lumen loss. These results suggest that RR inhibition may be an effective new tool for the treatment of atheroproliferative disorders.
机译:诸如动​​脉粥样硬化的人类增生性疾病是重要的健康问题,并且是美国发病率和死亡率的主要原因之一。微创治疗程序,包括带支架部署的血管成形术,经常用于阻塞性冠状动脉疾病。然而,再狭窄,一种增生性血管反应,是该手术的常见后遗症。当前的研究研究了抑制核糖核苷酸还原酶(RR)(一种细胞增殖所必需的酶)的作用,以试图改善增殖反应。选择了两种RR抑制剂Didox和羟基脲,因为它们具有强大的抗增殖特性。通过使用双重伤害的兔子模型进行研究,在该模型中,内皮剥脱后再给予高脂饮食。在最初的内皮剥脱术后第4周,对发展中的动脉粥样硬化病变进行腔内球囊扩张术,以模拟经皮腔内血管成形术的临床干预。再狭窄和动脉粥样硬化的程度在8周评估。病变的组织学评估表明,用去氧丁酸和羟基脲治疗可显着减少病变面积和管腔损失。这些结果表明,RR抑制可能是治疗动脉粥样硬化增生性疾病的有效新工具。

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