Department of Internal Medicine 1, National Defense Medical College, Saitama, Japan.
J Atheroscler Thromb. 2011;18(11):1009-17. doi: 10.5551/jat.9324. Epub 2011 Sep 24.
The anti-oxidant enzyme copper/zinc superoxide dismutase (CuZnSOD) metabolizes superoxide anion (O(2)(-)) in vascular cells. However, the role of CuZnSOD in vascular injury remains poorly understood.
Using CuZnSOD-deficient (CuZnSOD(-/-)) mice and wild-type (WT) mice, we investigated morphometric changes and the role of O(2)(-) in vascular remodeling after femoral artery injury induced by an external vascular cuff model.
Three days post-injury, inflammatory cell infiltration increased significantly. Moreover, the percent positive area of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in media were higher in CuZnSOD(-/-) mice than in WT mice (TNF-α: 34.8±8.4% versus 18.8±5.6%, p < 0.05, ICAM-1: 29.6±6.5% versus 11.0±2.8%, p < 0.05, VCAM-1: 23.5±7.5% versus 3.7±1.1%, p < 0.05). mRNA expression of iNOS was markedly increased in CuZnSOD(-/-) mice with cuff injury. Dihydroethidine staining revealed increased levels of vascular O(2)(-) in media from CuZnSOD(-/-) mice. Although neointimal formation remained unchanged, 14 days postinjury, we observed degeneration of the media, and the media/vessel wall ratio increased in CuZnSOD(-/-) mice (40.4±2.1% versus 26.8±1.4%, p < 0.05). Furthermore, SMemb/MHC-B-stained lesions increased markedly in CuZnSOD(-/-) mice.
CuZnSOD-deficiency promoted inflammation, expressed adhesion molecules, and altered the structure of the media post-injury. Our results suggest that O(2)(-) participates importantly in the progression of early stage vascular inflammation, resulting in vascular remodeling in media but not neointimal formation, post-injury.
抗氧化酶铜/锌超氧化物歧化酶（CuZnSOD）在血管细胞中代谢超氧阴离子（O(2)(-))。然而，CuZnSOD 在血管损伤中的作用仍知之甚少。
使用 CuZnSOD 缺陷（CuZnSOD(-/-)）小鼠和野生型（WT）小鼠，我们通过外部血管套管模型诱导的股动脉损伤，研究了形态计量学变化以及 O(2)(-)在血管重构中的作用。
损伤后 3 天，炎症细胞浸润明显增加。此外，CuZnSOD(-/-)小鼠中 TNF-α、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）在血管中层的阳性面积百分比高于 WT 小鼠（TNF-α：34.8±8.4%比 18.8±5.6%，p < 0.05，ICAM-1：29.6±6.5%比 11.0±2.8%，p < 0.05，VCAM-1：23.5±7.5%比 3.7±1.1%，p < 0.05）。 cuff 损伤后，CuZnSOD(-/-)小鼠中 iNOS 的 mRNA 表达明显增加。二氢乙啶染色显示 CuZnSOD(-/-)小鼠血管中层 O(2)(-)水平升高。尽管新生内膜形成无变化，但损伤后 14 天，我们观察到中层变性，CuZnSOD(-/-)小鼠的中层/血管壁比增加（40.4±2.1%比 26.8±1.4%，p < 0.05）。此外，CuZnSOD(-/-)小鼠中 SMemb/MHC-B 染色病变明显增加。
CuZnSOD 缺陷促进了损伤后炎症、表达黏附分子和中层结构的改变。我们的结果表明，O(2)(-) 重要参与了早期血管炎症的进展，导致损伤后血管中层的血管重塑，但不导致新生内膜形成。
