The Inhibition of Neointima Hyperplasia with 17-beta Estradiol Local Delivery in a Porcine Coronary Stent Restenosis Model

Lee, Sang Hyun; Kim, Weon; Jeong, Myung Ho; Park, Ok Young; Kim, Jung Ha; Kim, Ju Han; Lim, Sang Yup; Shim, Doo Sun; Moon, Jae Youn; Hong, Young Joon; Ahn, Young Keun; Park, Jong Tae; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

Abstract

Estradiol (17-beta-estradiol) is not only related to improvement in endothelial function such as regeneration of injured endothelial cells, platelet aggregation, and monocyte migration but also plays a major role in stabilizing atheromatous plaques by inhibiting migration and proliferation of smooth muscle cells. This study was performed to assess effects of locally transmitted estradiol on neointimal hyperplasia after stenting in a porcine coronary stent restenosis model. Two vessels were randomly selected in each of eight pigs and 1 mg of estradiol was locally administered through Dispatch CatheterTM in one coronary artery (group I) and control saline solution in the other coronary artery (group II). The pigs were sacrificed four weeks later and quantitative coronary angiographic and histopathologic analysis were performed. Laboratory findings before and after the procedure were within normal range and not different between both groups except for the serum estradiol level: 10.0+/-0.2 pg/ml before the procedure and 472.9+/-473.4 pg/ml one hour after the procedure. On histopathologic examination the vascular injury score was not different between both groups. The neointimal area was 1.2+/-1.90 mm2 in group I and 2.2+/-1.30 mm2 in group II (p<0.05) and the histopathologic stenosed area was 24.9+/-1.51% in group I and 36.7+/-1.15% in group II (p<0.05). However, endothelialization score, intimal fibrin deposit, intimal vascularity and adventitial fibrosis were not different between both groups. Local estradiol delivery is effective in inhibiting neointimal hyperplasia in a porcine coronary stent restenosis model, but further study will be required to find out the underlying mechanism.