Wang Kai, Kessler Paul D, Zhou Zhongmin, Penn Marc S, Forudi Farhad, Zhou Xiaorong, Tarakji Khaldoun, Kibbe Melina, Kovesdi Imre, Brough Douglas E, Topol Eric J, Lincoff A Michael
Experimental Animal Laboratory, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA.
Mol Ther. 2003 May;7(5 Pt 1):597-603. doi: 10.1016/s1525-0016(03)00061-3.
In this study the effect of local adenoviral-mediated delivery of inducible nitric oxide synthase on restenosis was evaluated in a porcine coronary stented model. Local gene transfer of recombinant adenoviral vectors that encode human inducible nitric oxide synthase (AdiNOS) was tested. Control vector (AdNull) lacked a recombinant transgene. Endoluminal delivery of 1.0 x 10(11) adenoviral particles was accomplished in 45 s using the Infiltrator catheter (Interventional Technologies, San Diego, CA). Coronary stents were deployed, oversized by a ratio of 1.2:1, in the treated segments immediately after gene transfer. Fourteen animals were sacrificed at day 28 to evaluate the effects of iNOS gene transfer on morphometric indices, and 4 animals were sacrificed at day 4 for detection of human iNOS expression by RT-PCR. iNOS mRNA was detected in six of eight iNOS-transferred arteries, whereas no expression of human iNOS was detected in the nontarget arteries. Morphometric analysis showed that iNOS transfer significantly reduced neointimal formation (3.41 +/- 1.12 mm(2) vs 2.14 +/- 0.68 mm(2), P < 0.05). We concluded that efficient intramural adenovirus-mediated iNOS transfer can be achieved by using Infiltrator catheters. iNOS gene transfer significantly reduces neointimal hyperplasia following stent injury.
在本研究中，我们在猪冠状动脉支架置入模型中评估了局部腺病毒介导的诱导型一氧化氮合酶递送对再狭窄的影响。对编码人诱导型一氧化氮合酶（AdiNOS）的重组腺病毒载体进行了局部基因转移测试。对照载体（AdNull）缺乏重组转基因。使用Infiltrator导管（Interventional Technologies，圣地亚哥，加利福尼亚州）在45秒内完成了1.0×10¹¹个腺病毒颗粒的腔内递送。基因转移后立即在治疗节段置入冠状动脉支架，支架尺寸过大，比例为1.2:1。在第28天处死14只动物，以评估诱导型一氧化氮合酶基因转移对形态学指标的影响，在第4天处死4只动物，通过逆转录聚合酶链反应检测人诱导型一氧化氮合酶的表达。在8条接受诱导型一氧化氮合酶转移的动脉中有6条检测到诱导型一氧化氮合酶信使核糖核酸，而在非靶动脉中未检测到人类诱导型一氧化氮合酶的表达。形态学分析表明，诱导型一氧化氮合酶转移显著减少了新生内膜形成（3.41±1.12平方毫米对2.14±0.68平方毫米，P<0.05）。我们得出结论，使用Infiltrator导管可实现有效的壁内腺病毒介导的诱导型一氧化氮合酶转移。诱导型一氧化氮合酶基因转移显著减少了支架损伤后的新生内膜增生。
