Abstract 10670: Superoxide Dismutase Gene Delivery Inhibits Smooth Muscle Cell Proliferation, Migration, and Superoxide Production In Balloon Injured Carotid Artery
Background and Objective: Extracellular superoxide dismutase (EC-SOD) scavenges oxidative radicals. Hence, it protects tissues from oxidative stress, a major contributor to coronary events. EC-SOD has been implicated in regulation of vascular function and responses to oxidative stress. Coronary intervention damages arterial wall, activates inflammation and oxidative stress as well as vascular cell growth. This study aims at investigating the effect of EC-SOD on vascular smooth muscle cell (VSMC) proliferation, neointima formation and underlying molecular mechanisms.
Methods: Rat carotid artery was injured by balloon denudation, and then EC-SOD transduced with and without the hemagglutinating virus of Japan envelope vector (HVJ-E) carrying EC-SOD cDNA. Fourteen days after balloon injury, the carotid artery specimens were excised for H&E staining, immunohistochemistry (IHC) and RT-PCR studies. The impacts of EC-SOD gene therapy in the inhibition of VSMC proliferation, migration, and production of reactive oxygen species (ROS) were studied. The effects of EC-SOD in MEK1/2, ERK1/2 and Akt activations were also assessed by immunoblotting in primary cultured VSMCs.
Results: The intima-to-media area ratio of the EC-SOD transfected arteries (1.3±0.2, mean±SD) was significantly lower than that of the empty vector-transfected (2.3±0.3, p< 0.05) group. Also, EC-SOD significantly reduced the inflammatory cytokines as assessed by the TNF-α (p<0.01) and IL-1β (p=0.008) IHC. EC-SOD overexpression significantly inhibited VSMC proliferation, migration and ROS production. The expression and activation of MEK1/2, ERK1/2 and Akt after 10% fetal bovine serum and 20 ng/ml platelet-derived growth factor-BB (PDGF-BB) stimulations were significantly attenuated in the EC-SOD transfected group than the non-transfected or vector- transfected groups (p < 0.05 in all comparisons).
Conclusion: EC-SOD overexpression by HVJ-E gene delivery can inhibit VSMC proliferation and migration, decrease ROS production and inflammatory cytokine expression triggered by balloon injury. EC-SOD gene delivery also diminishes post-injury neointima hyperplasia. The inhibitory effects of EC-SOD may occur via suppression of MEK1/2, ERK1/2 and Akt signaling pathways.
- © 2013 by American Heart Association, Inc.