17 beta-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta

The aim of the present study was to investigate anti-proliferative and anti -atherogenic properties of 17 beta -estradiol in balloon injured female and male rabbit aortae. Thirty-two female and 32 male New Zealand White rabbit s where gonadectomised. Vascular injury was performed with a balloon cathet er in the lower abdominal aorta. Male and female rabbits were randomised in to four groups of eight animals each. Only two of four groups received a 0. 5% cholesterol-enriched diet. One cholesterol-diet group and one normal-die t group received intramuscular injections of estradiol valerate (1 mg/kg bo dy weight/week). After 28 days, the denuded part of the abdominal aorta was excised and analysed by morphometry and immunohistochemistry. Estrogen tre atment did not show an inhibitory effect on neointimal proliferation in nor mo-cholesterolemic male or female rabbits. A gender independent inhibitory effect of 17 beta -estradiol was seen on atheroma development in cholestero l-fed female and male rabbits, while plasma total cholesterol levels were s ignificantly reduced in male rabbits only. The 17 beta -estradiol treatment was associated with a significantly decreased number of luminal endothelia l cells in not-mo and hyper-cholesterolemic female rabbits, as evaluated by immunohistochemical staining for 'von Willebrand factor'. Staining for Ki- 67-positive proliferating cells after 28 days showed a statistically signif icant increased proliferative activity in the neointima of hyper-cholestero lemic female rabbits. The neointimal content of macrophages increased signi ficantly in all hyper-cholesterolemic rabbits. Under 17 beta -estradiol tre atment, the number of macrophages was increased in female and decreased in male rabbits by tendency. Additionally, the 'classical' vascular estrogen r eceptor was present in both female and male rabbit aortae without statistic ally significant differences. In conclusion, 17 beta -estradiol did not red uce post-injury neointima formation in normo-cholesterolemic rabbits. Howev er, in hyper-cholesterolemic rabbits, 17 beta -estradiol reduced atheroma d evelopment gender independently. This effect cannot be explained by lowerin g of plasma cholesterol levels or endothelium-mediated pathways, and requir es further investigation on, for example, antioxidative, antiproliferative or estrogen receptor mediated effects. (C) 2001 Elsevier Science Ireland Lt d. All rights reserved.