Inhibition of neointimal formation in porcine coronary artery by a Ras mutant.

Inhibition of neointimal formation in porcine coronary artery by a Ras mutant.
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Ras 突变体对猪冠状动脉新内膜形成的抑制。

DOI:
10.1006/jsre.2001.6159
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发表时间:
2001
期刊:
The Journal of surgical research.
影响因子:
--
通讯作者:
Chien,S
Chien,S
中科院分区:
--
文献类型:
--
作者:
Wu,CH;Lin,CS;Hung,JS;Wu,CJ;Lo,PH;Jin,G;Shyy,YJ;Mao,SJ;Chien,S

文献摘要

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背景减少球囊损伤引起的新生内膜形成的治疗方法主要集中在大鼠颈动脉再狭窄的实验模型上。然而,在大鼠颈动脉再狭窄可能不会复制冠状动脉损伤的反应在较大的动物和human.MethodsIn这项研究中,我们使用猪冠状动脉作为动物模型,以评估预防作用的病毒介导的显性负突变体RasN17球囊损伤引起的再狭窄。通过调度导管将病毒颗粒递送到球囊损伤的冠状动脉,以使病毒在受限的动脉段中保持10分钟以达到最佳转染。球囊损伤后6周,猪被处死,左前降支动脉被分离的组织学analysis.ResultsNeointima形成是突出的组接受球囊损伤相比,未受伤的对照组。在损伤的冠状动脉中也发现了胶原迁移的重塑过程。AdRasN17的应用导致新生内膜形成减少56%,管腔大小增加75%,相比与AdLacZ control.ConclusionsThese结果表明,AdRasN17是一种有效的治疗基因,在防止球囊损伤诱导的猪冠状动脉新生内膜形成。
BackgroundTherapeutic approaches to reduce the neointimal formation caused by balloon injury have been focused mainly on experimental models of restenosis in the rat carotid artery. However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger animals and humans.MethodsIn this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative mutant RasN17 on balloon injury-induced restenosis. The viral particles were delivered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection. Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analysis.ResultsNeointima formation was prominent in the group receiving balloon injury as compared with the uninjured controls. A remodeling process with migration of collagen was also found in the injured coronary arteries. The application of AdRasN17 led to a 56% decrease in neointima formation and a 75% increase in lumen size, as compared with the balloon-injured vessels treated with AdLacZ control.ConclusionsThese results suggest that AdRasN17 is an effective therapeutic gene in preventing balloon injury-induced neointimal formation in pig coronary arteries.