Inhibition of estrogen receptor function promotes porcine coronary artery smooth muscle cell proliferation.
Estradiol-17beta (E2) can inhibit vascular smooth muscle cell (VSMC) proliferation probably through its ability to activate its nuclear estrogen receptors (ER). Activation or inhibition of the ER by cognate permissive or non-permissive ligands, respectively, would indicate whether ER action is critical for this vascular protective effect. We investigated a previously characterized population of cultured porcine coronary artery SMCs for ER expression and for the response of these cells to estrogens and antiestrogens. Reverse transcription-polymerase chain reaction and Western blot analyses demonstrated ER mRNA and protein, respectively, in these cells. While the culture conditions required may have prevented the demonstration of physiological effects of E2, the antiestrogens, ICI 182,780 and 4-hydroxytamoxifen, stimulated VSMC proliferation. The data suggest that, by interrupting ER function, antiestrogens significantly increased the VSMC mitotic rate. This model may be used to identify ER-regulated genes that function to control the growth of these coronary artery SMCs.
Lavigne
M C
MC
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA.
Ramwell
P W
PW
Clarke
R
R
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D017931:DNA Primers; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000235:genetics; D013552:Swine; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol