Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury.

Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury.
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脂质体介导的动脉基因转移后基因表达增加,与内膜平滑肌细胞增殖相关。

DOI:
10.1172/jci117017
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发表时间:
1994
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Isner,JM
Isner,JM
中科院分区:
--
文献类型:
--
作者:
Takeshita,S;Gal,D;Leclerc,G;Pickering,JG;Riessen,R;Weir,L;Isner,JM

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动脉基因转移是一种新的策略,是潜在的适用于各种心血管疾病。使用非病毒载体进行动脉基因转移的尝试已经受到低转染效率的影响。我们研究了动脉损伤诱导的细胞增殖在脂质体介导的基因转移后可以增加基因表达的假设。将未裸露和裸露的兔动脉条保持在培养物中长达21 d,之后用编码萤火虫荧光素酶的质粒和阳离子脂质体的混合物进行转染。在非裸露动脉中,转染前的培养间隔不影响基因表达。相比之下,转染前培养3-14天的裸露动脉的表达量高出7-13倍(与第0天相比; P < 0.005)。然后在有或没有预先血管成形术的情况下,对活兔的髂动脉进行经皮转染。血管成形术后3-7 d转染基因表达增加(P < 0.05)。在体外通过[3 H]胸苷掺入和在体内通过增殖细胞核抗原免疫染色评估新生内膜细胞的增殖活性,与基因表达平行增加和下降。因此,这些研究结果表明,脂质体介导的动脉基因转移的表达可能会在存在持续的细胞增殖的情况下增强。图片
Arterial gene transfer represents a novel strategy that is potentially applicable to a variety of cardiovascular disorders. Attempts to perform arterial gene transfer using nonviral vectors have been compromised by a low transfection efficiency. We investigated the hypothesis that cellular proliferation induced by arterial injury could augment gene expression after liposome-mediated gene transfer. Nondenuded and denuded rabbit arterial strips were maintained in culture for up to 21 d, after which transfection was performed with a mixture of the plasmid encoding firefly luciferase and cationic liposomes. In non-denuded arteries, the culture interval before transfection did not affect the gene expression. In contrast, denuded arteries cultured for 3-14 d before transfection yielded 7-13-fold higher expression (vs. day 0; P < 0.005). Transfection was then performed percutaneously to the iliac arteries of live rabbits with or without antecedent angioplasty. Gene expression increased when transfection was performed 3-7 d postangioplasty (P < 0.05). Proliferative activity of neointimal cells assessed in vitro by [3H]thymidine incorporation, and in vivo by immunostaining for proliferating cell nuclear antigen, increased and declined in parallel with gene expression. These findings thus indicate that the expression of liposome-mediated arterial gene transfer may be augmented in presence of ongoing cellular proliferation.Images
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