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(Circulation. 1997;96:927-933.)
© 1997 American Heart Association, Inc.

Articles

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

Hong Lou, MD; Yejun Zhao, MD; Patrick Delafontaine, MD; Teruaki Kodama, MD; Nevin Katz, MD; Peter W. Ramwell, PhD; ; Marie L. Foegh, MD, DSc

From Georgetown University Medical Center, Washington, DC, and Emory University School of Medicine (P.D.), Atlanta, Ga.

Correspondence to Marie L. Foegh, MD, DSc, Georgetown University Medical Center, 4000 Reservoir Rd, NW, Bldg D, Rm 397, Washington, DC 20007. E-mail mfoegh{at}aol.com

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 [³H]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<.02). Smooth muscle cells were derived from the native aorta of the placebo-treated rabbits to study the effect of estradiol in vitro. IGF-I increased cell counts in a concentration-dependent manner. In serum-starved cells estradiol further decreased cell proliferation; this effect was blocked by the specific estrogen receptor antagonist ZK-119.010. Immunohistochemistry staining for IGF-I protein in the coronary arteries and ascending aorta of the cardiac allograft from the placebo-treated recipients revealed extensive IGF-I expression in the myointima. In contrast, IGF-I protein was not expressed in the coronary arteries and ascending aorta of the cardiac allograft from the estradiol-treated recipients. The IGF-I protein was extensively expressed only in the placebo-treated graft vessels. Myointimal thickening of the coronary arteries was significantly reduced by estradiol treatment (17.9±1.5% versus 44.3±3.7%; P<.02).

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.

Key Words: transplantation • hormones • coronary disease • muscle, smooth • immunohistochemistry

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