Estrogen Effects on Insulin-Like Growth Factor-I (IGF-I)–Induced Cell Proliferation and IGF-I Expression in Native and Allograft Vessels

Background Estrogen protects against cardiovascular disease in both patients and animal models and regulates insulin-like growth factor-I (IGF-I), an important cell-cycle progression factor. Methods and Results Smooth muscle cells and tissues were harvested from male recipient rabbits that 6 weeks earlier had received a cardiac allograft transplant consisting of a donor heart and ascending aorta. Segments of the ascending aorta from the native and allograft hearts from 9 placebo-treated and 8 estradiol-treated recipients were compared by using IGF-I–stimulated [ 3 H]thymidine incorporation. The responses of the native vessel segments were similar (175.3±32% and 166.9±41%, respectively; P >.05) whether or not the recipients had been treated for 6 weeks with estradiol. In the grafts, however, estradiol markedly inhibited vascular cell thymidine incorporation (328.04±56% compared with 67.3±11%; P P Conclusions In vivo estradiol treatment abolishes both IGF-I mitogenic effects and IGF-I protein expression in the vascular wall, which may be causally related to the inhibitory effect of estradiol on transplant arteriosclerosis.