title: Estrogen effects on insulin-like growth factor-I (IGF-I)-induced cell proliferation and IGF-I expression in native and allograft vessels.
abstract: 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.
  
  
  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.
authors.affiliation: Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lou
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Delafontaine
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: N
authors.initials: N
authors.lastname: Katz
authors.forename: P W
authors.initials: PW
authors.lastname: Ramwell
authors.forename: M L
authors.initials: ML
authors.lastname: Foegh
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001158:Arteries; D002455:Cell Division / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D016027:Heart Transplantation; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D008934:Mitogens; D004958:Estradiol; D007334:Insulin-Like Growth Factor I