Eplerenone suppresses neointimal formation after coronary stent implantation in swine

Background Enhanced extracellular matrix accumulation rather than cell proliferation contributes to later stages of in-stent restenosis. Aldosterone itself has been shown to increase cardiovascular fibrosis, therefore, we studied the suppressive effects of eplerenone, a new aldosterone receptor antagonist, on neointimal hyperplasia after coronary stent implantation in swine. Methods Palmatz-Shatz stents were implanted in the left anterior descending artery of 36 pigs. One hundred milligrams of Eplerenone was orally administered from 1 week before, to 4 weeks after stent implantation in Group E (n = 18), and vehicle was given to Group C (n = 18). Pigs were sacrificed 1 or 4 weeks after stent implantation. The number of infiltrating macrophages was calculated at 1 week. Morphometrical analysis was performed to measure the area of each layer, and %area of fibrosis and mRNA for collagen I, III and TGF-β was analyzed by RT-PCR at 4 weeks. Results The number of infiltrating macrophages was less in Group E than in Group C (p < 0.01). The overall size of coronary arteries at 4 weeks was similar in both groups. However, the luminal area was larger in Group E than in Group C (p < 0.05), and the intimal area was smaller in Group E than in Group C (p < 0.05). The %area of fibrosis was significantly less in Group E than in Group C at 4 weeks (p < 0.01). In Group E, the expression of mRNA for collagen I, III and TGF-β was significantly reduced. Conclusion Orally administered eplerenone attenuated collagen accumulation within the neointima, thereby inhibiting neointimal hyperplasia after stent implantation.