Deficiency of CuZn superoxide dismutase promotes inflammation and alters medial structure following vascular injury

Abstract

Aim: The anti-oxidant enzyme copper/zinc superoxide dismutase (CuZnSOD) metabolizes superoxide anion (O2-) in vascular cells. However, the role of CuZnSOD in vascular injury remains poorly understood. Methods: Using CuZnSOD-deficient (CuZnSOD-/-) mice and wild-type (WT) mice, we investigated morphometric changes and the role of O2- in vascular remodeling after femoral artery injury induced by an external vascular cuff model. Results: 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 O2- 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. Conclusions: CuZnSOD-deficiency promoted inflammation, expressed adhesion molecules, and altered the structure of the media post-injury. Our results suggest that O2- participates importantly in the progression of early stage vascular inflammation, resulting in vascular remodeling in media but not neointimal formation, post-injury.