Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.
Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.
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兔模型中的经皮动脉基因转移。
DOI：
10.1172/jci115970
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Isner,JM
中科院分区：
文献类型：
--
作者：
Leclerc,G;Gal,D;Takeshita,S;Nikol,S;Weir,L;Isner,JM
通过分析兔模型的转染效率，研究了采用完全经皮策略将外源DNA传递到正常和球囊扩张的动脉粥样硬化动脉的可能性。采用双球囊-导管系统，用荧光素酶表达载体质粒和脂质体溶液转染22只兔（正常10只，动脉粥样硬化12只）的22条髂外动脉。转染片段的分析显示22条动脉中有10条荧光素酶活性（4/10正常vs 6/12球囊损伤动脉粥样硬化，P = NS）；作为对照的对侧肢体动脉段未检测到任何活动。成功转染片段的荧光素酶活性水平测量为4.10 +/- 1.19 （m +/- SEM）特纳光单位（TLU），正常人为3.03 +/- 1.16 TLU，而气球损伤的动脉粥样硬化动脉为4.81 +/- 1.87 TLU （P = NS）。成功转染的动脉粥样硬化切片的原位杂交显示，来自罕见细胞（少于1/ 1000）的荧光素酶基因mRNA的表达仅限于新内膜病变。因此，新的遗传物质的表达可以在正常和球囊扩张的动脉粥样硬化动脉中实现。然而，当前递送策略的低效率代表了一个潜在的限制，如果该策略要应用于人类血管疾病的治疗方法，必须加以改进。图片
The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.Images