Local resistance to oxidative stress by overexpression of copper-zinc superoxide dismutase limits neointimal formation after angioplasty

Michael D. Kuo, Isaac J. Bright, David S. Wang, Paras Ghafouri, Eser Yuksel, Paul R. Hilfiker, Douglas N. Miniati, Michael D. Dake

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD). Methods: The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing β-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation. Results: At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation by-products were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582±0.088 for the nonviral control group versus 0.565±0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259±0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05). Conclusions: Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)585-594
Number of pages10
JournalJournal of Endovascular Therapy
Volume11
Issue number6
DOIs
Publication statusPublished - Dec 1 2004
Externally publishedYes

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Keywords

  • Antioxidants
  • Atherosclerosis
  • Extracellular matrix
  • Free radicals
  • Inflammation
  • Lipid peroxidation
  • Rabbit model
  • Restenosis
  • Smooth muscle cells
  • Superoxide dismutase

ASJC Scopus subject areas

  • Surgery
  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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