Inhibition of neointimal hyperplasia in a rabbit vein graft model following non-viral transfection with human iNOS cDNA.
Inhibition of neointimal hyperplasia in a rabbit vein graft model following non-viral transfection with human iNOS cDNA.
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作者：
隐静脉冠状动脉旁路移植术后新生内膜增生引起的静脉移植衰竭是一个重要的临床问题。缺乏安全有效的血管基因转移载体严重阻碍了这一领域的进展。为此，我们开发了受体靶向纳米复合物（Receptor-Targeted Nanocomplex， RTN）载体系统，并在兔静脉旁路移植术模型中评估了其治疗效果。第7天，β-半乳糖苷酶的体外递送显示广泛转染贯穿静脉壁，估计约占外膜和介质细胞的10%。然后用编码诱导型一氧化氮合酶（iNOS）的质粒转染静脉移植物，并将其植入颈动脉。对术后7天死亡的家兔标本进行荧光免疫组化分析，结果显示转染的主要是内皮细胞和巨噬细胞。从28天组的静脉移植样本的形态计量学分析显示，与手术对照组相比，inos治疗组的新内膜厚度减少了约50%，新内膜面积减少了64%。本研究证实了通过RTN配方递送iNOS基因对兔移植静脉疾病模型IH的降低作用。
Vein graft failure caused by neointimal hyperplasia (IH) after coronary artery bypass grafting with saphenous veins is a major clinical problem. The lack of safe and efficient vectors for vascular gene transfer has significantly hindered progress in this field. We have developed a Receptor-Targeted Nanocomplex (RTN) vector system for this purpose and assessed its therapeutic efficacy in a rabbit vein graft model of bypass grafting. Adventitial delivery of β-Galactosidase showed widespread transfection throughout the vein wall on day 7, estimated at about 10% of cells in the adventitia and media. Vein grafts were then transfected with a plasmid encoding inducible nitric oxide synthase (iNOS) and engrafted into the carotid artery. Fluorescent immunohistochemistry analysis of samples from rabbits killed at 7 days after surgery showed that mostly endothelial cells and macrophages were transfected. Morphometric analysis of vein graft samples from the 28-day groups showed approximately a 50% reduction of neointimal thickness and 64% reduction of neointimal area in the iNOS-treated group compared with the surgery control groups. This study demonstrates efficacy of iNOS gene delivery by the RTN formulation in reducing IH in the rabbit model of vein graft disease.
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影响因子：
3.4
作者：
Kolh, Philippe;Wijns, William;Taggart, David
通讯作者：
Taggart, David
影响因子：
3.7
作者：
Mann, M J
通讯作者：
Mann, M J
影响因子：
4.2
作者：
Muhs, A;Heublein, B;Von der Leyen, HE
通讯作者：
Von der Leyen, HE
影响因子：
5.1
作者：
Akowuah, EF;Gray, C;Newman, CM
通讯作者：
Newman, CM
DOI：
10.1152/ajpheart.00760.2003
发表时间：
2004-01-01
影响因子：
4.8
作者：
Jiang, ZH;Wu, LZ;Berceli, SA
通讯作者：
Berceli, SA