Effect of Rosuvastatin on Bovine Pericardial Aortic Tissue Valve Calcification in a Rat Subdermal Implantation Model

Abstract

Background and ObjectivesThere are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of this study was to examine the effects of statin treatment on calcification in bovine pericardial tissue valves.Materials and MethodsForty Sprague-Dawley rats were randomly divided into 4 groups according to hypercholesterolemia induction and statin intake (Group 1, n=10: normal diet without statin treatment, Group 2, n=10: normal diet with statin treatment, Group 3, n=10: high fat diet without statin treatment, Group 4, n=10: high fat diet with statin treatment). Serum lipid levels were measured just before the experiment and after 4 and 12 weeks. Bovine pericardial tissue valve cusps were surgically implanted in rat dorsal subcutis at 4 weeks. After the surgery, statin was administered daily to Groups 2 and 4. Serum interleukin-6 (IL-6) level was measured at 5 weeks. Cusps were explanted at 12 weeks and calcium levels were determined by atomic absorption spectroscopy.ResultsMean IL-6 was significantly higher in Group 3 at 5 weeks (7.14, 2.03, 31.70, and 6.90 pg/dL for each group, respectively). Mean calcium level in Group 3 was significantly higher among groups but Group 4 was significantly lower compared to Group 3 and was similar to Group 1, 2 (1.86, 1.92, 2.55, and 1.80 mg/g for each group, respectively, p<0.01).ConclusionHypercholesterolemia may be a significant risk factor for bovine pericardial valve calcification. Statin treatment significantly attenuated calcification of bovine pericardial valve tissue in a rat subdermal implantation model and might prolong the durability of bioprostheses.

Rosuvastatin attenuates bioprosthetic heart valve calcification

“…8,9 In our previous study, we evaluated, in a rat subdermal implantation model, the effects of a specific statin therapy, rosuvastatin (Crestor, HMG-CoA reductase inhibitor, rosuvastatin calcium, AstraZeneca Pharmaceuticals LP, Gaithersburg, Md), on postimplantation tissue changes in a commonly used bovine aortic valve bioprosthesis. 10 Our results suggested that the statin could significantly attenuate the calcification of the bioprosthesis in a rat subdermal implantation model and might thereby prolong the durability of the bioprosthesis. However, only 1 type of bioprosthetic valve (a Carpentier-Edwards Perimount aortic valve, Irvine, Calif) was used in our previous experiment, so we did not obtain information about a range of commonly used tissue valves.…”

“…Our previous pilot study investigated the effect of rosuvastatin on the calcification of bovine pericardial aortic tissue valves in a rat subdermal implantation model. 10 The principal finding of that study was that high cholesterol levels may be a significant risk factor for bovine pericardial valve calcification. Statin treatment was able to significantly attenuate calcification of bovine pericardial valves in a subcutaneous rat model and had the dual effect of anticalcification and anti-inflammation regardless of hypercholesterolemia.…”

“…Moreover, our results indicated that statin treatment can prevent postimplant calcification and inflammatory infiltration in an animal model. 10 It has been reported that cholesterol deposition may play an important role in long-term structural valve degeneration even in individuals with normal lipid profiles. The deposition of LDL-C particles on the external surface of the valve leaflets initiates a chronic inflammatory reaction, which, over a long period of time, leads to calcification, scarring, and leaflet dysfunction.…”

Effect of Vitamin D on YKL-40: Rat Hypercholesterolemia Model

“…The 25(OH)VitD values in our study are consistent with the studies in the literature with a similar nutritional pattern. 11) 12) 15) …”

Commentary: Tissue valves—One more reason to stay on top of your cholesterol

“…Indeed, in this group's previous work, they found no statin effect in rats with normal cholesterol. 4 Still, it is quite meaningful that researchers studying valve calcification in laboratory animals use hypercholesterolemia to accelerate valve failure. 5 This relationship between cholesterol and valve calcification has similarly been identified in human studies.…”