Extracellular superoxide dismutase overexpression reduces cuff-induced arterial neointimal formation
Extracellular superoxide dismutase overexpression reduces cuff-induced arterial neointimal formation
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DOI：
10.1016/j.atherosclerosis.2005.01.051
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发表时间：
2005-07-01
期刊：
影响因子：
5.3
通讯作者：
Nakashima, Y
中科院分区：
文献类型：
--
作者：
Ozumi, K;Tasaki, H;Nakashima, Y
套囊损伤模型中新生内膜形成的机制尚不清楚。为了研究细胞外超氧化物歧化酶（EC-SOD）是否可以减少袖带损伤模型中的新生内膜形成，将表达EC-SOD（AxCAEC-SOD）或大肠杆菌β-半乳糖苷酶（AxCALacZ）的腺病毒注射到大鼠股动脉袖带和外膜之间。其结果是，EC-SOD蛋白有效地产生外膜，通过免疫组化染色进行评估。与袖带处理的对照动脉和AxCALacZ转染的动脉相比，AxCAEC-SOD转染的动脉中新生内膜形成显著减少。此外，EC-SOD处理的新生内膜和中膜中增殖的平滑肌细胞减少。EC-SOD处理后，血管壁iNOS表达增加，细胞凋亡减少，胶原含量减少。通过二氢乙锭染色和腔肠素化学发光评估，EC-SOD表达减少了组织中活性氧（ROS）的产生。这些结果表明，活性氧，特别是超氧阴离子在外膜，是负责在袖口损伤模型的新生内膜形成。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The mechanisms of neointimal formation in cuff-injury models are still uncertain. To examine whether extracellular superoxide dismutase (EC-SOD) can reduce neointimal formation in a cuff-injury model, adenoviruses expressing EC-SOD (AxCAEC-SOD) or Escherichia coli beta-galactosidase (AxCALacZ) was injected between the cuff and the adventitia of rat femoral arteries. As a result, EC-SOD protein was effectively produced in the adventitia, as assessed by immunohistochemical staining. In comparison with cuff-treated control arteries and AxCALacZ-transfected arteries, neointimal formation was significantly reduced in AxCAEC-SOD-transfected arteries. Furthermore, proliferating smooth muscle cells in neointima and media were reduced by EC-SOD treatment. Similarly, augmented iNOS expression, apoptosis and collagen content in the vascular wall were also reduced by EC-SOD treatment. Reactive oxygen species (ROS) generation in tissue was reduced by EC-SOD expression, as assessed by dihydroethidium staining and coelenterazine chemiluminescence. These results suggest that ROS, especially superoxide anions at an adventitia, are responsible for neointimal formation in a cuff-injury model. (c) 2005 Elsevier Ireland Ltd. All rights reserved.