Local delivery of 17β-estradiol improves reendothelialization and decreases inflammation after coronary stenting in a porcine model

Abstract

In the current study, we investigated the effect of local intravascular delivery of 17beta-estradiol (17beta-E) on subsequent in-stent neointimal hyperplasia. Twenty-seven stents were implanted in coronary arteries of juvenile swine. Coronary arteries were randomized to local treatment with 17beta-E or no drug therapy (control-vehicle treated). Twenty-eight days post-treatment, angiographic images revealed an improved minimal lumen diameter (2.2 +/- 0.2 vs. 1.3 +/- 0.2 mm, P < 0.005) and a reduction of late lumen loss (1.7 +/- 0.2 vs. 2.3 +/- 0.1 mm, P < 0.01) in 17beta-E-treated vessels compared to control-vehicle treated. Histological analyses showed a reduction of stenosis (51.49 +/- 6.75 vs. 70.86 +/- 6.24%, P < 0.05), mean neointimal thickness (0.51 +/- 0.07 vs. 0.83 +/- 0.14 mm, P < 0.05) and inflammation score (1.29 +/- 0.28 vs. 2.85 +/- 0.40, P < 0.05) in 17beta-E-treated arteries compared to control-vehicle treated arteries. Immunohistochemistry analyses revealed a reduction of proliferating smooth muscle cells and increased in-stent reendothelialization in 17beta-E-treated arteries. Finally, we observed a correlation between neointimal hyperplasia and inflammation score, which in turn, was inversely related to reendothelialization. Locally delivered, 17beta-E is inhibiting the inflammatory response and smooth muscle cells proliferation and improving vascular reendothelialization which together are contributing to reduce in-stent restenosis in a porcine coronary injury model. Together, these data demonstrate the potential clinical application of 17beta-estradiol to improve vascular healing and prevent in-stent restenosis.