Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model

BACKGROUND Neointimal hyperplasia is an important mechanism of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Systemically administered estrogen is known to inhibit neointimal formation after arterial injury. OBJECTIVES We sought to assess the efficacy of locally delivered 17-beta-estradiol (BE) in inhibiting neointimal hyperplasia after PTCA. METHODS Eighteen juvenile farm pigs were studied. Coronary angioplasty was performed in all three coronary arteries of each animal. After PTCA, each coronary artery in each pig was randomized to receive either local delivery of 600 μg BE, vehicle alone or PTCA only. Twelve animals were euthanized at 28 days for morphometric analysis, and four animals were euthanized at seven days for immunohistochemical analysis of vascular smooth muscle cell (SMC) proliferative activity. Two animals died a few days after PTCA and were excluded. RESULTS On morphometric study, the arterial segments treated with BE demonstrated significantly less neointimal proliferation. Arteries treated with BE had reductions in several indexes of restenosis compared with arteries treated with vehicle alone or PTCA only: neointimal area (0.4 ± 0.09 mm2 for BE vs. 1.14 ± 0.33 mm2 for vehicle alone vs. 0.88 ± 0.2 mm2 for PTCA only, p < 0.05), percent neointima (12.16 ± 2.57% vs. 25.46 ± 4.73% vs. 23.02 ± 3.97%, p < 0.025), neointima/media area (0.59 ± 0.14 vs. 1.75 ± 0.41 vs. 1.67 ± 0.43, p < 0.01) and restenotic index (1.3 ± 0.14 vs. 2.42 ± 0.22 vs. 2.4 ± 0.23, p < 0.005). Immunohistochemistry showed decreased SMC proliferative activity in BE-treated arteries compared with the other two treatment groups (p < 0.05). CONCLUSIONS Local delivery of BE significantly decreases neointimal hyperplasia after PTCA in pigs, probably by the inhibition of SMC proliferation