Objectives: The role of oxidative stress in the degeneration of biological cardiovascular grafts
has not been clarified yet. Therefore, the present study aimed at developing a rat
model for the examination of the degeneration of aortic conduit implants under enhanced
oxidative stress conditions.
Methods: Genetically modified rats suffering from superoxide dismutase 3 (Group SOD) deficiency
(n = 24) underwent infrarenal implantation of cryopreserved native aortic conduits,
while SOD3-competent recipient animals served as controls (n = 28). After 4 or 12 weeks, the grafts were explanted and analyzed for markers of
degeneration and oxidative stress.
Results: SOD3-deficient rats presented decreased circulating SOD activity (p < 0.01), whereas the superoxide load in the grafts was enhanced only by trend. At
12 weeks, the relative expression of Runx2 (2.3 ± 0.5 versus 1.1 ± 0.2; p < 0.05), osteopontin (1.8 ± 0.5 versus 1.1 ± 0.1; p = 0.14), αSMA (1.8 ± 0.4 versus 1.2 ± 0.2; p = 0.16), SOD1 and dysfunctional SOD3 was increased or enhanced by trend in SOD3 mutants
as compared with controls, while inflammatory markers (TGFβ1, TNFα, Il1β) were not
upregulated.
Conclusion: In biological cardiovascular grafts, functional SOD3 deficiency in our rat model
seems to result in compensatory upregulation of SOD1. Nevertheless, typical markers
of osteogenic transformation may indicate slowly progressing graft degeneration. Long-term
studies are required to evaluate the significance of these findings in terms of graft
durability.
