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 complication in long-term survivors of cardiac transplantation. Estrogen prevents transplant arteriosclerosis in experimental cardiac and aortic allografts and may act by an immune mechanism. Methods and Results: New Zealand White rabbits immunosuppressed with cyclosporine were recipients of cardiac allografts from Dutch Belted rabbits. The recipients received either estradiol or placebo daily until they were killed 6 weeks later. Histological cross sections of the cardiac allograft were used for quantification of major histocompatibility complex (MHC) class II antigen expression, T lymphocytes, and macrophages by immunohistochemistry using monoclonal antibodies, MHC class II antigen expression was not delectable 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 artery myointima was significantly less frequent in the estradiol-treated group. Rejection was moderate but slightly less in the estradiol-treated group. These findings were associated with a 60% decrease in allograft coronary artery myointimal thickening (determined by morphometry) in the estradiol-treated compared with the placebo-treated group. Conclusions: Estradiol treatment of cardiac allograft recipients abolishes MHC class II antigen expression in the coronary arteries and decreases macrophage infiltration in all three layers of the vessel wall, whereas T-lymphocyte infiltration is decreased only in the myointima. These findings are associated with estradiol inhibition of myointimal proliferation. Thus, estradiol treatment may have a beneficial effect on graft arteriosclerosis through immune mechanisms.