Abstract
Male New Zealand White rabbits fed a 0.5% cholesterol diet (n = 13) received a heterotopic cardiac allograft and cyclosporine ( 10 mg/kg/day) until sacrifice 6 to 7 weeks later, at which time both the native and transplanted hearts and aorta were harvested. Six of the rabbits were treated with estradiol 100 μg/kg/day i.m., beginning 7 days prior to transplantation and continuing until sacrifice; the remaining seven rabbits served as controls and received placebo. The native aorta as well as the aorta from the grafted hearts were isolated and used for in vitro studies involving cytokine and growth factor stimulated cell proliferation. Tritiated thymidine incorporation is expressed as CPM/mg protein and the changes in cell proliferation are expressed as % changes from the control (the unstimulated vessel). IGF-I and IL-6 but not interferon-γ (INF-γ) significantly increased cell proliferation, measured as 3 H-thymidine incorporation. in explants from both native and allograft vessels and significantly more so in the graft (p < 0.05). The mitogenic effect of both IGF-I and IL-6 in the graft aorta, but not in that associated with the native heart, was abrogated by chronic treatment with estradiol (p < 0.02). % Change in Vascular Wall Cell Proliferation IGF-I (20 μg/ml) INF-γ (50 U/ml) IL-6 (50 U/ml) Native - Estradiol 175 ± 32 189 ± 43 162 ± 28 + Estradiol 167 ± 42 143 ± 79 159 ± 36 Allograft - Estradiol 328 ± 66 197 ± 56 366 ± 101 + Estradiol 64 ± 12 116 ± 41 72 ± 14 Mean ± SEM This inhibitory effect of estradiol treatment on the mitogenic effect of IGF-I and IL-6 on the vascular wall of the allograft supports previous studies showing that accelerated coronary transplant arteriosclerosis in this model is inhibited by estrogen. These data speak to the use of hormone replacement therapy in post menopausal women receiving a cardiac transplant.
Published Version
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