Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.
Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.
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抑制新内膜血管病变的基因治疗：内皮细胞一氧化氮合酶基因的体内转移。
DOI：
10.1073/pnas.92.4.1137
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发表时间：
1995
影响因子：
11.1
通讯作者：
Dzau,VJ
中科院分区：
文献类型：
--
作者：
vonderLeyen,HE;Gibbons,GH;Morishita,R;Lewis,NP;Zhang,L;Nakajima,M;Kaneda,Y;Cooke,JP;Dzau,VJ
据推测，血管疾病涉及调节血管张力和结构的因素的稳态平衡的紊乱。基因转移技术的最新发展已成为治疗血管疾病的令人兴奋的治疗选择。几项研究已经确定了通过使用β-半乳糖苷酶或荧光素酶等报告基因将体内基因直接转移到脉管系统中的可行性。迄今为止，还没有研究记录编码功能性酶的 cDNA 的体内基因转移的治疗效果。这项研究检验了以下假设：内皮源性一氧化氮是血管病变形成的内源性抑制剂。大鼠颈动脉内皮球囊损伤后，采用高效仙台病毒/脂质体体内基因转移技术，恢复了血管壁内皮细胞一氧化氮合酶（ec-NOS）的表达。 ec-NOS 基因转染不仅将 NO 产量恢复到正常未治疗血管中的水平，而且还增加了受损血管的血管反应性。球囊损伤后第 14 天的新内膜形成被抑制了 70%。这些发现提供了直接证据，表明NO是体内血管病变形成的内源性抑制剂（通过抑制平滑肌细胞增殖和迁移），并表明ec-NOS转染作为治疗新内膜增生的潜在治疗方法的可能性。
It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as beta-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessels. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.