Abstract :
Effect of E2F Decoy Oligodeoxynucleotides Gene Therapy on Intimal Hyperplasia in Autogenous Vein Graft of Dogs
Song Ok Lee, M.D., Won Hyun Cho, M.D.
Department of Surgery,
Keimyung University School of Medicine, Daegu, Korea
Key Words :
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Fig. 1. E2F decoy transfection under nondistending pressure.
Fig. 2. Autogenous interposition vein graft at a defected femoral artery.
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Fig. 3. Effect of E2F decoy on dog aorta smooth muscle cell proliferation. Marked suppression of aortic smooth muscle cell proliferation was noted in D which contains E2F decoy compare with group B, C and E (p < 0.01).
A: normal glucose, 5.5 m b: High glucose (HG), 22 m C: HG + 10% FBS; D: HG + 10% FBS + E2F decoy; E: HG + 10% FBS + mismatched oligodeoxynucleotides.
Fig. 4. Light microscopic appearance of vascular anastomotic vein site. Marked suppression of the intimal hyperplasia was showed in E2F decoy-treated group compared with heparin-treated group or mismatched oligodeoxynucleotides (ODN)-treated group. There was no difference between group 2 and 3. Group 1: heparin treated, 4 months after bypass; Group 2: E2F treated, 4 weeks after bypass; Group 3: E2F treated, 4 months after bypass; Group 4: mismatched ODN treated, 4 months after bypass. Arrows indicate location of internal elastic lamina. I: intima; IEL: internal elastic lamina; M: media (H&E stain, original magnification 100).
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Fig. 5. Elastic stain of vascular anastomotic vein site. Marked suppression of the intimal hyperplasia was showed in E2F decoy-treated group compare with heparin-treated group or mismatched ODN-treated group. There was no difference between group 2 and 3. Group 1: heparin treated, 4 months after bypass; Group 2: E2F treated, 4 weeks after bypass; Group 3: E2F treated, 4 months after bypass; Group 4: mismatched ODN treated, 4 months after bypass. Arrows indicate location of internal elastic lamina. I: intima; IEL: internal elastic lamina; M:
media (Elastic stain, original magnification 100).
Table 1. Intima/media area ratio of proximal and distal anastomotic site of grafted vein
Group 1: heparin treated, 4 months after bypass (n = 3); Group 2: E2F treated, 4 weeks after bypass (n = 3); Group 3: E2F treated, 4 months after bypass (n = 4); Group 4: mismatched ODN treated, 4 months after bypass (n = 4). Group 1 vs Group 3 vs Group 4: p = 0.000, Group 2 vs 3: p = 0.446, Proximal vs distal anastomotic site: p = 0.934.
Group 1 Group 2 Group 3 Group 4
Proximal 1.59 0.31 0.19 0.28 0.22 0.13 1.66 0.31
Distal 1.39 0.29 0.54 0.36 0.29 0.08 1.55 0.27
Total 1.49 0.29 0.37 0.32 0.26 0.11 1.61 0.28
Fig. 6. Proliferating cell nuclear antigen (PCNA) expression in autogenous vein interposition graft at a defected femoral artery treated with heparin, E2F decoy ODN, or mismatched ODN. Expression of PCNA was suppressed in the autografts transfected with E2F decoy. There was no difference between group 2 and 3. Group 1: heparin treated, 4 months after bypass; Group 2: E2F treated, 4 weeks after bypass; Group 3: E2F treated, 4 months after bypass; Group 4: mismatched ODN treated, 4 months after bypass. PCNA-positive cells stained as brownish-black color (Immunohistochemical stain with PCNA antibody, original magnification 200).
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