E2F Decoy Oligodeoxynucleotides on Neointimal Hyperplasia in Canine Vein Graft

Abstract

Double-stranded DNA with high affinity to E2F as a decoy cis-element blocks the activation of genes mediating the cell cycle, resulting in effective suppression of the smooth muscle cell proliferation that causes intimal hyperplasia. To evaluate the effect of the E2F decoy to suppress neointimal hyperplasia autogenous venous bypass grafts were performed in dogs after incubation with heparin (group 1), with E2F decoy oligodeoxynucleotides (ODN) (groups 2 and 3), or with a random ODN (group 4) using a Japan-liposomeal method based on a hemagglutinating virus. The intimal and medial cross-sectional surface area of the anastomotic site was measured at 4 months after bypass surgery in groups 1, 3, and 4 by computerized planimetry and at 4 weeks in group 2 to compare the intimal/medial (I/M) area ratios. Autogenous vein grafts treated with E2F decoy showed a significant reduction in I/M area ratio (0.26± 0.11) compared with the heparin-treated control group (1.49 ± 0.29) or the mismatched ODN-treated group (1.61 ± 0.28; P = .000). There was no difference in the I/M area ratio according to experimental periods (groups 2 vs 3: 0.26 ± 0.11 vs 0.37 ± 0.32; P =.446) or the anastomotic sites (proximal vs distal; P = .934). In conclusion, an E2F decoy can suppress neointimal hyperplasia in autogenous vein grafts, which may prolong patency by reducing graft stenosis.