Key result
In a rat model of accelerated cardiovascular calcification, simvastatin failed to diminish the calcification of decellularized aortic conduit implants compared to a pro-calcific diet alone.
Why the study?
All present biological cardiovascular prostheses are prone to progressive in vivo degeneration, and the potential additional beneficial effect of statins on decellularized implants was unknown.
Does simvastatin prevent calcification of decellularized aortic conduit implants in a rat model of accelerated cardiovascular calcification?
Does simvastatin prevent calcification of decellularized aortic conduit implants in a rat model of accelerated cardiovascular calcification?
In a rat model, simvastatin did not diminish the calcification of decellularized aortic conduit implants despite lowering LDL cholesterol.
Animal data on statins for decellularized implants are hypothesis-generating; leaves open clinical translation and durability benefit.
BACKGROUND: All present biological cardiovascular prostheses are prone to progressive in vivo degeneration, which can be partially impaired by decellularization. The administration of statins may provide an additional beneficial effect. We provide the first in vivo data on the effect of statins on decellularized cardiovascular implants. METHODS: Wistar rats with aortic valve insufficiency (day 14) were fed either with a pro-calcific diet (group C; n = 17), or the same diet additionally supplemented with simvastatin (group S; n = 16). Aortic conduits from Sprague-Dawley rats were detergent-decellularized, infrarenally implanted (day 0) in all recipients and explanted at day 28 or day 84. RESULTS: Sonographic competence of the conduit perfusion was 100%, and overall survival amounted to 97%. Simvastatin decreased the low-density lipoprotein cholesterol serum levels; however, it did not affect the calcification of the implants. Histology revealed alpha-smooth muscle actin-positive intima hyperplasia in both groups. Extensive matrix metalloproteinase activity was observed in calcified areas, especially in group S. Quantitative RNA analysis resulted in no differences with regard to several markers of calcifying degeneration (alkaline phosphatase, osteopontin, osteocalcin, osteoprotegerin, bone morphogenetic protein-2, runt-related transcription factor-2) and inflammation (tumor necrosis factor α, interleukin 1β, receptor for advanced glycation end products, CD39, CD73), but significantly lower levels of interleukin-6 in group S. CONCLUSIONS: In a standardized small animal model of accelerated cardiovascular calcification, simvastatin failed to diminish the calcification of decellularized aortic conduit implants. This finding confirms the observations of recent clinical trials. However, further experiments are warranted to elucidate the value of partial benefits associated with lower circulating lipid and proinflammatory cytokine levels.
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Assmann et al. (2014) studied Aortic valve insufficiency (n=33). Simvastatin vs. Pro-calcific diet alone was evaluated on Calcification of the implants. In a rat model of accelerated cardiovascular calcification, simvastatin failed to diminish the calcification of decellularized aortic conduit implants compared to a pro-calcific diet alone.
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