Journal
FASEB JOURNAL
Volume 36, Issue 11, Pages -Publisher
WILEY
DOI: 10.1096/fj.202200727RR
Keywords
aortic valve graft; calcification; graft degeneration; oxidative stress; superoxide dismutase-3
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Funding
- S. Bunnenberg Foundation
- Projekt DEAL
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This study provides evidence that oxidative stress plays a role in the degeneration of biological cardiovascular grafts. Rats deficient in superoxide dismutase 3 showed decreased antioxidant activity and exhibited regurgitation, intima hyperplasia, and calcification in the implanted grafts.
While oxidative stress is known as key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not been clarified yet. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of biological cardiovascular allografts in a standardized chronic implantation model realized in rats exhibiting superoxide dismutase 3 deficiency (SOD3((-))). Rats with SOD3 loss-of-function mutation (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3-competent recipients served as controls (n = 28). After a follow-up period of 4 or 12 weeks, comparative analyses addressed degenerative processes, hemodynamics, and evaluation of the oxidative stress model. SOD3((-)) rats presented decreased circulating SOD activity (p = .0079). After 12 weeks, 58% of the implant valves in SOD3((-)) rats showed regurgitation (vs. 31% in controls, p = .2377). Intima hyperplasia and chondro-osteogenic transformation contributed to progressive graft calcification (p = .0024). At 12 weeks, hydroxyapatite deposition (p = .0198) and the gene expression of runt-related transcription factor-2 (Runx2) (p = .0093) were significantly enhanced in group SOD3((-)). This study provides the first in vivo evidence that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.
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