Degeneration biologischer Herzklappen in einem SOD3-Defizienz-Ratten-Modell

While oxidative stress is known as a key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not yet been clarified. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of cardiovascular allografts in a standardized chronic implantation model in genetically modified rats exhibiting superoxide dismutase 3 deficiency (SOD3⁽⁻⁾; loss of function mutation). The SOD3⁽⁻⁾ rats (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3-competent recipient rats served as controls (n = 28). After a follow-up observational period of 4 or 12 weeks, comparative analyses were carried out to address degenerative processes, hemodynamics and evaluation of the oxidative stress model. The SOD3⁽⁻⁾ rats presented decreased serum SOD activity (p = 0.0079). After 12 weeks 58% of the implanted valves in SOD3⁽⁻⁾ rats showed regurgitation (vs. 31% in control animals, p = 0.2377). Progressive intimal hyperplasia and chondro-osteogenic transformation contributed to a massive graft calcification (p = 0.0024). At 12 weeks, hydroxyapatite deposition (p = 0.0198) and the gene expression of runt-related transcription factor 2 (RUNX2, p = 0.0093) were significantly enhanced in the SOD3⁽⁻⁾ group. The results of this study provide first in vivo indications that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.