Estrogen inhibits vascular smooth muscle cell-dependent adventitial fibroblast migration in vitro.
BACKGROUND
Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo. Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was designed to establish a mechanism whereby estrogen attenuates migration of adventitial fibroblasts. METHDS AND RESULTS: Primary cultures of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restricted to early-passage VSMCs. Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experimental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast migration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration. In contrast, treatment of VSMCs with 17beta-estradiol (10(-9) to 10(-7) mol/L) before preconditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17beta-estradiol and the ER antagonist ICI-182780 (10(-7) mol/L) blocked the inhibitory effect of estrogen on fibroblast migration.


CONCLUSIONS
These observations suggest a novel mechanism of hormonal vasoprotection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechanism.
Li
G
G
University of Alabama at Birmingham, Department of Medicine, Division of Transplantation, Chicago, ILL, USA.
Chen
Y F
YF
Greene
G L
GL
Oparil
S
S
Thompson
J A
JA
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002339:Carotid Arteries / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005355:Fibrosis; D000077267:Fulvestrant; D017930:Genes, Reporter; D009097:Multienzyme Complexes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D011138:Polytetrafluoroethylene; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000096:biosynthesis; D017154:Stromal Cells / Q000166:cytology; D014945:Wound Healing
D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D009097:Multienzyme Complexes; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D011138:Polytetrafluoroethylene; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases