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Background: The type 3 superoxide dismutase (SOD3) has been considered as a protective enzyme against the development of atherosclerosis. This study evaluated whether recombinant baculoviral vector-mediated SOD3 gene delivery has a protective effect on neointima formation, vascular inflammation, reactive oxygen species (ROS) elimination, and exploring the cell growth signaling pathways.
Methods and Results: The SOD3 cDNA containing recombinant baculovirus or vAcMBac-CMV-IE-SOD3 was initially constructed. Rat carotid artery was injured by balloon denudation, and then vAcMBac-CMV-IE-SOD3 was delivered to the injured carotid arteries. Hematoxylin and eosin staining of arterial section showed a significant reduction of the intima-to-media area ratio in the SOD3 transfected arteries (0.63 ± 0.02) compared to that in the control arteries (1.28 ± 0.11, p< 0.01). The immunohistochemistry images showed that overexpression of SOD3 down-regulated the balloon injury-induced NF-κB expression. Another in-vitro experiment studied the impact of expression of SOD3 in antioxidant, anti-proliferation and anti-migration in the primary vascular smooth muscle cells (VSMCs). Comparing with control groups, vAcMBac-CMV-IE-SOD3 transfected group significantly inhibited 10% FBS- (P<0.05) and 20 ng/ml PDGF-BB-(p<0.001) induced ROS productions detected by flow cytometer. Significant anti-proliferation and anti-migration effects in the SOD3 transfected group were also noted by XTT and wound healing assays, respectively (p<0.05 in all comparisons). SOD3 overexpression of the VSMC cultures demonstrated that the activation of MEK1/2, ERK1/2 and Akt were significantly attenuated in the SOD3 transfected group (p< 0.05 in all comparisons) using the immunoblotting assay.
Conclusions: SOD3 overexpression using a novel recombinant baculoviral vector significantly inhibits the neointima formation and vascular inflammation, and attenuates the ROS production, and proliferation and migration of VSMCs, which suggest the beneficial effect of SOD3 in regulation of restenosis. The inhibitory effects of SOD3 may occur via modulation of the MEK1/2, ERK1/2 and Akt signaling pathways.
Moderated Poster Contributions
Vascular Medicine Moderated Poster Theater, Poster Hall, Hall C
Sunday, March 19, 2017, 12:30 p.m.-12:40 p.m.
Session Title: Mechanisms of Vascular Inflammation in Atherogenesis
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1320M-03
- 2017 American College of Cardiology Foundation