A Rat Model to Examine the Degeneration of Cardiovascular Grafts under Enhanced Oxidative Stress

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.