Estrogen decreases neointimal hyperplasia and improves re-endothelialization in pigs

17-Beta-estradiol inhibits smooth muscle cell proliferation and migration and accelerates endothelial cell repair in response to balloon injury. The aim of this study was to determine whether administration of estrogen is associated with decreased neointimal hyperplasia after stenting in the porcine model.

Twenty-two farm female pigs 7 months old were oophorectomized and at the third day normal saline (11 pigs) or 20 mg of estradiol valerate (11 pigs), modified release, were administered intramuscularly. At the 10th day after oophorerectomy, 1 or 2 stainless steel stents were implanted in the right coronary artery in each pig, and at the 17th day, normal saline or 10 mg estradiol valerate, modified release, were administered intramuscularly in the two groups. Pigs were sacrificed 28 days after stent implantation and histomorphometric analysis of the coronary arteries was performed (20 stents from the estrogen and 18 stents from the control groups). In the estrogen group, neointimal proliferation area was 1.42+/-0.55 mm(2), whereas in the control group, 1.96+/-0.89 mm(2) (p=0.02). Area stenosis was 39+/-13% and 49+/-16% in the two groups, respectively (p=0.07). Re-endothelialization was 2.67+/-0.34 and 2.22+/-0.46 in the two groups, respectively (p<0.010). The injury score was similar between the two groups.

These data suggest that intramuscular administration of estrogen accelerates the endothelial cell repair in response to injury and reduces intimal hyperplasia in the porcine model.