Abstract 3534: Insufficiency of DNA Repair Pathway in Human Vein Graft with Early Graft Failure
Objectives: The mechanisms of early vein graft failure after coronary artery bypass graft (CABG) surgery remains unclear. We hypothesized that insufficiency of DNA repair pathway in human vein graft is related to early graft failure.
Methods: Human internal mammary arteries (IMA) and saphenous veins (SV) samples were obtained from coronary artery bypass grafting surgery. Among 118 SV segments, there was 9% vein grafts had early grafting failure within 7 days which is determined by Multichannel-EKG-gated CT angiography (Philips Medical). In contrast, there was no early graft failure in 28 IMA grafts. Human IMA or SV segments (1 X 1 mm) were incubated in organ culture system in the absence or presence of 1% H2O2 for 24 hours with 20% O2. DNA damage was determined by 8-oxoG staining, and DNA repair pathways were investigated by MYH (DNA mismatch repair) immunohistochemical staining. Apoptotic level was evaluated by TUNEL staining and DNA gel analysis. The positive staining rate was determined by [positive nuclear/total 1000 nuclear x 100%]. Apoptosis-inducing factor (AIF) and caspase-3 was investigated by immunochemistry and Western blot analysis.
Results: Table 1⇓ demonstrates DNA damage-repair and apoptosis of IMA and SV in the absence (control) or presence of oxidative stress (1% H2O2 in 24h incubation). (Mean ± SEM; *P<0.05 versus SV Control Group; †P<0.05 versus IMA Control Group; ‡P<0.05 versus IMA (1% H2O2) Group). DNA repair enzyme MYH level was higher in IMA compared with that in SV following oxidative stress. Furthermore, DNA damage (8-oxoG) and apoptosis (TUNEL) as well as apoptosis-related genes (AIF and Cas-3) were markedly increased in failure SV segments compared with IMA and non-failure SV segments following oxidative stress.
Conclusions: This study suggested that insufficiency of DNA repair pathway in SV grafts following oxidative stress maybe one of important mechanisms contributes to early vein graft failure after CABG surgery.