INHIBITION OF TRANSPLANT CORONARY ARTERIOSCLEROSIS IN RABBITS BY CHRONIC ESTRADIOL TREATMENT IS ASSOCIATED WITH ABOLITION OF MHC CLASS-II ANTIGEN EXPRESSION

Background Accelerated coronary arteriosclerosis is a major complicati on in long-term survivors of cardiac transplantation. Estrogen prevent s transplant arteriosclerosis in experimental cardiac and aortic allog rafts and may act by an immune mechanism. Methods and Results New Zeal and White rabbits immuno-suppressed with cyclosporine were recipients of cardiac allografts from Dutch Belted rabbits. The recipients receiv ed either estradiol or placebo daily until they were killed 6 weeks la ter. Histological cross sections of the cardiac allograft were used fo r quantification of major histocompatibility complex (MHC) class II an tigen expression, T lymphocytes, and macrophages by immunohistochemist ry using monoclonal antibodies. MHC class II antigen expression was no t detectable in allograft coronary arteries from any of the estradiol- treated recipients, whereas this antigen expression was present in the allograft coronary arteries from all the placebo-treated recipients. Macrophage and lymphocyte infiltration of the allograft coronary arter y myointima was significantly less frequent in the estradiol-treated g roup. Rejection was moderate but slightly less in the estradiol-treate d group. These findings were associated with a 60% decrease in allogra ft coronary artery myointimal thickening (determined by morphometry) i n the estradiol-treated compared with the placebo-treated group. Concl usions Estradiol treatment of cardiac allograft recipients abolishes M HC class II antigen expression in the coronary arteries and decreases macrophage infiltration in all three layers of the vessel wall, wherea s T-lymphocyte infiltration is decreased only in the myointima. These findings are associated with estradiol inhibition of myointimal prolif eration. Thus, estradiol treatment may have a beneficial effect on gra ft arteriosclerosis through immune mechanisms.