Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells.
The present study was performed to elucidate the mechanism underlying the anti-atherogenic action of estrogen. We investigated the effect of estrogen on intimal thickening of the rat femoral artery induced by cuff placement and further examined the effect of estrogen on migration and proliferation of vascular smooth muscle cells (VSMCs) in culture. Intimal thickening was significantly greater in males than in control females. Intimal thickening in females was increased to the level in males by ovariectomy. Estrogen replacement to ovariectomized rats reversed this effect. Proliferating cell nuclear antigen immunohistochemistry showed that in vivo proliferation of VSMCs contributed to the difference in intimal thickening. There was no difference in blood pressure and serum lipids, suggesting that estrogen directly acted on artery and inhibited intimal thickening. 17 beta-Estradiol (E2, 1-100 nmol/l) inhibited migration of cultured rat VSMCs, assayed using a microchemotaxis chamber, in a concentration-dependent manner. E2 (0.01-100 nmol/l), but not progesterone or testosterone, also inhibited [3H]thymidine incorporation in rat VSMCs in a concentration-dependent manner. Indomethacin, NG-monomethyl-L-arginine and methylene blue did not influence the inhibitory action of E2 on [3H]thymidine incorporation, suggesting that prostanoids and nitric oxide are not involved in the action of E2. E2 did not provoke VSMC injury, as measured by the release of incorporated [3H]2-deoxy-D-glucose. These results suggest that the inhibition of migration and proliferation of VSMCs contributes to the inhibitory effect of estrogen on intimal thickening.
Akishita
M
M
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Ouchi
Y
Y
Miyoshi
H
H
Kozaki
K
K
Inoue
S
S
Ishikawa
M
M
Eto
M
M
Toba
K
K
Orimo
H
H
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003847:Deoxyglucose / Q000378:metabolism; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000166:cytology / Q000187:drug effects* / Q000601:surgery; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D010052:Ovariectomy; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008055:Lipids; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D004247:DNA; D003847:Deoxyglucose; D011464:Epoprostenol; D013936:Thymidine; D007213:Indomethacin