| Effect of E2F Decoy
Oligodeoxynucleotides Gene Therapy on
Intimal Hyperplasia in Autogenous Vein Graft of Dogs |
| 실험견에서 E2F Decoy 전이가 자가정핵 이식견의 내막과형성에 미치는 영향 |
|
이성억; 조원현 |
|
|
|
|
| Abstract |
|
One of the leading causes of
coronary and peripheral vascular graft failure is intimal hyperplasia at the vascular anastomotic site. Double-stranded DNA with high affinity for E2F as decoy cis elements may block the activation of genes mediating the cell cycle; suggesting that it could possibly be an effective therapeutic agent for treating intimal hyperplasia. In order to evaluate the effect of E2F decoy in a large animal model; jugular vein to femoral artery interposition grafts in experimental dogs with 15-20 kg body weight were treated; with either heparin; E2F decoy oligodeoxynucleotides (ODN) or mismatched ODN by hemagglutinating virus of Japan (HVJ) -liposome method using pressure-mediated delivery. The animals were divided into four groups; depending on the method of treatment and duration of observation. Group 1 (n= 3): heparin treated; four months after bypass; Group 2 (n= 3): E2F treated; four weeks after bypass; Group 3 (n= 4): E2F treated; four months after bypass; and Group 4 (n= 4): mismatched ODN treated; four months after bypass. Computerized planimetry was used to measure intimal and medial cross-sectional surface areas of each vessel. The intima/media area ratios were compared between the groups after bypass surgery. Treatment of grafts with E2F decoy resulted in a significant reduction of intimal thickness after four months (intima/media area ratio= 0.26 ± 0.11) compared with mismatched ODN-treated group (intima/media area ratio= 1.61 ± 0.28) or heparin alone group (intima/media area ratio=1.49 ± 0.29) (p= 0.000). There was no difference between group 2 (0.37 ± 0.32) and 3 (0.26 ± 0.11) and between proximal and distal anastomotic sites. The above results suggest that gene therapy of E2F decoy in vein graft could be a new therapeutic strategy to prolong the graft patency by suppressing the intimal hyperplasia. |
| Key Words:
E2F decoy,
Intimal hyperplasia |
PDF Links
Full text via DOI
Download Citation
