Inhibitory effect of low-dose estrogen on neointimal formation after balloon injury of rat carotid artery.
The current regimens of hormone replacement therapy for postmenopausal women, estrogen combined with progestogen, have failed to show beneficial effects for the prevention of atherosclerotic disease. Although the relatively higher dose of estrogen contained in those regimens exerted adverse effects, there are few data examining a lower dose of estrogen in an atherosclerosis model. Therefore, we investigated experimentally whether lower doses of estrogen could inhibit neointimal formation after balloon injury of the rat carotid artery. Ten-week-old Wistar rats were subjected to ovariectomy or sham-operation (n=7). Four days after ovariectomy, rats were implanted with an osmotic mini-pump containing 17-beta estradiol (0.2, 1, 2, 10 and 20 microg/kg/day; n=6, 4, 8, 6 and 5, respectively) or placebo (n=10). After 3 days of hormone therapy, balloon injury was performed in the left common carotid artery. Neointimal formation was histologically evaluated 2 weeks after injury. Cross-sectional intimal area and the ratio of intimal area to medial area were dose-dependently reduced by estrogen replacement compared with those in ovariectomized rats without estrogen replacement. The effects of estrogen replacement were identical to those of an angiotensin II type 1 receptor blocker, candesartan. Interestingly, the effect was significant even in rats receiving lower doses of estrogen, in which plasma estradiol concentrations were not increased and the hyperplastic response of the uterus was minimal. These results suggest the efficacy of low-dose estrogen therapy for the protection of atherosclerosis.
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Tokumitsu
T
Watanabe
Yukiko
Y
Miyahara
Masahiro
M
Akishita
Takashi
T
Nakaoka
Naohide
N
Yamashita
Katsuya
K
Iijima
Hong
H
Kim
Koichi
K
Kozaki
Yasuyoshi
Y
Ouchi
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D004967:Estrogens