GENETIC-ENGINEERING OF VEIN GRAFTS RESISTANT TO ATHEROSCLEROSIS
GENETIC-ENGINEERING OF VEIN GRAFTS RESISTANT TO ATHEROSCLEROSIS
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DOI：
10.1073/pnas.92.10.4502
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发表时间：
1995-05-09
影响因子：
11.1
通讯作者：
DZAU, VJ
中科院分区：
文献类型：
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作者：
MANN, MJ;GIBBONS, GH;DZAU, VJ
以前，研究人员推测基因工程可以改善血管移植物的长期功能，这些血管移植物容易发生动脉粥样硬化和闭塞，在这项研究中，我们证明了使用反义寡脱氧核苷酸阻断中膜平滑肌细胞增殖的术中基因治疗方法可以预防加速动脉粥样硬化，这是自体静脉移植物失败的原因，选择性阻断两种细胞周期调节蛋白，增殖细胞核抗原和细胞分裂周期2激酶的基因表达，在兔颈静脉平滑肌细胞移植到颈动脉中实现。这种基因表达的改变成功地将静脉移植物生物学从新生内膜增生转向中膜肥大，产生更接近正常动脉的管道。更重要的是，这些基因工程移植物被证明对饮食诱导的动脉粥样硬化具有抗性。这些发现确立了开发基因工程生物假体的可行性，这些生物假体具有抗失效性，更适合于闭塞性血管疾病的长期治疗。
Previously, researchers have speculated that genetic engineering can improve the long-term function of vascular grafts which are prone to atherosclerosis and occlusion, In this study, we demonstrated that an intraoperative gene therapy approach using antisense oligodeoxynucleotide blockage of medial smooth muscle cell proliferation can prevent the accelerated atherosclerosis that is responsible for autologous vein graft failure, Selective blockade of the expression of genes for two cell cycle regulatory proteins, proliferating cell nuclear antigen and cell division cycle 2 kinase, was achieved in the smooth muscle cells of rabbit jugular veins grafted into the carotid arteries. This alteration of gene expression successfully redirected vein graft biology away from neointimal hyperplasia and toward medial hypertrophy, yielding conduits that more closely resembled normal arteries, More importantly, these genetically engineered grafts proved resistant to diet-induced atherosclerosis. These findings establish the feasibility of developing genetically engineered bioprostheses that are resistant to failure and better suited to the long-term treatment of occlusive vascular disease.