17 beta-estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males.
OBJECTIVE
Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17 beta-estradiol on SMC proliferation and migration.


METHODS
SMC were cultured from saphenous veins of postmenopausal women and age-matched men. Cell growth was determined by 3H-thymidine incorporation and cell counting. Migration of SMC was assessed in 4-well chambers. SMC were seeded in one corner and PDGF-BB in filter paper glued onto the opposite wall.


RESULTS
PDGF-BB (5 ng/ml for 24 h) similarly stimulated 3H-thymidine incorporation in female (511 +/- 57%; n = 8) and male (528 +/- 62%; n = 12) SMC. This was reduced by 17 beta-estradiol (10(-8)-10(-6) M; female 313 +/- 52%; male 337 +/- 54%; P < 0.05). PDGF-BB increased the number of SMC (P < 0.0001 at 10 days) obtained from females (153 +/- 3%; n = 5) and males (150 +/- 4%; n = 5), which was inhibited by 17 beta-estradiol (10(-6) M; female 134 +/- 7%; male 128 +/- 5%; P < 0.05). Similar results were obtained with basic fibroblast growth factor. In contrast to 17 beta-estradiol, another steroid (dexamethasone) had no effects on 3H-thymidine incorporation in these cells stimulated with PDGF-BB, PDGF-BB (0.01-1 ng) stimulated SMC migration (P < 0.05) which was inhibited by 17 beta-estradiol (10(-10)-10(-6) M; n = 5; P < 0.005).


CONCLUSIONS
17 beta-Estradiol inhibits growth-factor-induced SMC proliferation and migration regardless of gender. These effects of 17 beta-estradiol may contribute to its cardiovascular protective properties in postmenopausal women during replacement therapy.
Dai-Do
D
D
Department of Cardiovascular Research, University Hospital, Bern, Switzerland.
Espinosa
E
E
Liu
G
G
Rabelink
T J
TJ
Julmy
F
F
Yang
Z
Z
Mahler
F
F
Lüscher
T F
TF
D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017698:Postmenopause / Q000502:physiology*; D012501:Saphenous Vein
D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D004958:Estradiol