Effects of adenoviral up-regulation of bcl-2 on oxidative stress and graft coronary artery disease in rat heart transplants

Douglas N. Miniati, Maarten A. Lijkwan, Seiichiro Murata, Jasper Martens, Caroline T. Coleman, E. Grant Hoyt, Robert C. Robbins

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background. Bcl-2 has been shown to have antioxidant properties. Early oxidative stress is an important antigen-independent factor that contributes to the development of graft coronary artery disease (GCAD). We hypothesized that adenoviral up-regulation of bcl-2 would decrease early oxidative stress and inhibit GCAD after heart transplantation. Methods. PVG rat hearts were treated with adenovirus carrying the human bcl-2 gene (AdvBcl-2) or null adenovirus (AdvNull) then transplanted into the abdomens of PVG recipients. After 4 days of reperfusion to allow adenoviral gene expression, grafts were retransplanted into ACI rat recipients and reperfused for 4 or 8 hours or 90 days (cyclosporine A 7.5 mg/kg on post-operative day [POD] 0-9). Production of tumor necrosis factor (TNF)-α after 4 hours and oxidized glutathione (GSSG) after 8 hours indicated development of oxidative stress. 90-day allografts were assessed for GCAD by way of computerized morphometry. Results. Over-expression of bcl-2 at the time of allograft reperfusion was confirmed by Western blotting. Whereas AdvNull-treated hearts demonstrated elevated TNF-α levels after 4 hours and increased GSSG after 8 hours of reperfusion, AdvBcl-2-treated hearts were no different from nontransplanted hearts. AdvBcl-2 treatment also resulted in decreased luminal narrowing and intima-to-media ratio at POD 90. Conclusions. Bcl-2 over-expression interrupts the development of oxidative stress in reperfused rat-heart allografts. Early up-regulation of bcl-2 also decreases GCAD, indicating the importance of early oxidative stress and the role that bcl-2 may play in the long-term function of heart transplants.

Original languageEnglish (US)
Pages (from-to)382-386
Number of pages5
Issue number2
StatePublished - Jul 27 2003
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation


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