Abstract 2480: Tacrolimus-eluting Stent Inhibits the Neointimal Hyperplasia in a Porcine Coronary Model by the Inhibition of Calcineurin Expression
Background: Tacrolimus (FK506) is a water-insoluble macrolide immunosuppressant with potent anti-inflammatory properties. Tacrolimus binds to the intracellular FK-binding protein, forms a complex, and then binds to calcineurin. This binding inhibits the activation of calcineurin. In addition, cell culture experiments indicated that tacrolimus could allow earlier endothelial regeneration than sirolimus. Therefore, tacrolimus is a promising new candidate for stent coating. The purpose of this study is to evaluate the efficacy of tacrolimus-eluting stent (TES) on neointimal hyperplasia in a porcine coronary model and clarify the mechanism for anti-restenosis effect.
Methods: TES is coated with a biodegradable polymer containing tacrolimus. Juvenile swine underwent balloon overstretch injury and were subjected to implantation of either bare metal stent (BMS) or TES. Histomorphometry was performed at 12 weeks after stenting, and immunohistochemistry was performed at 2, 4, and 12 weeks after stenting.
Result: At 12 weeks after stenting, TES showed less neointimal area (TES: 2.60±0.12 mm2 vs. BMS: 5.69±0.80 mm2, P<0.05) and less % area stenosis (TES: 37.6±6.3% vs. BMS: 62.5±17.5%, P<0.05) compared with BMS. Immunohistochemical staining demonstrated that calcineurin was not expressed in the medial smooth muscle cells (SMC) of non-injured coronary artery and it was up-regulated in the medial SMC at 2 weeks and the medial and neointimal SMC at 4 and 12 weeks after stenting in the BMS group. In contrast, in the TES group, the protein expression of calcineurin was inhibited in the medial SMC at 2 weeks and medial and neointimal SMC at 4 weeks after stenting.
Conclusion: This is the first report to demonstrate that calcineurin was up-regulated in-stent restenosis and TES inhibited its expression in a porcine coronary model. TES is suggested to be useful for reducing in-stent neointimal hyperplasia by the inhibition of calcineurin expression.