Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity
Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity
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DOI：
10.1161/01.atv.20.4.964
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发表时间：
2000-04-01
影响因子：
8.7
通讯作者：
Keller, PJ
中科院分区：
文献类型：
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作者：
Dubey, RK;Jackson, EK;Keller, PJ
一些雌激素类化合物可以改变血管平滑肌细胞(SMC)的生物学特性；然而，这种作用是否部分由雌激素受体介导尚不清楚。本研究的目的是评估临床使用的雌激素对人主动脉SMC生物学的作用是否由雌激素受体介导。我们研究了在雌激素受体拮抗剂ICI182,780存在和不存在的情况下，各种临床使用的雌激素对培养的人主动脉SMC DNA合成([H-3]胸腺嘧啶核苷掺入)、细胞增殖(细胞计数)、细胞迁移(改良的Boyden小室)、胶原合成([H-3]Pro掺入)和丝裂原活化蛋白激酶活性的影响。生理浓度的17β-雌二醇和低浓度(10-8~10-7mol/L)的17β-雌二醇、戊酸雌二醇组、己二醇组和苯甲酸雌二醇组均可显著抑制胎牛血清诱导的DNA合成、细胞增殖、胶原合成、血小板衍生生长因子诱导的SMC迁移和丝裂原活化蛋白激酶活性，但雌酮、雌三醇、17α-雌二醇和硫酸雌酮对此无明显影响。17β-雌二醇和其他抑制性雌激素的抑制作用可被100MU/L ICI182,780完全逆转，并且各种雌激素对SMC生物学的抑制作用与其对雌激素受体的秩序亲和力相匹配，雌激素对SMC生物学的抑制作用部分是由受体介导的，因为激素替代治疗的心脏保护作用很可能是通过改变SMC生物学来实现的，激素替代治疗是否对绝经后妇女心血管疾病具有保护作用将部分取决于雌激素与血管SMC上雌激素受体的亲和力。
Some estrogenic compounds modify vascular smooth muscle cell (SMC) biology; however, whether such effects are mediated in part by estrogen receptors is unknown. The purpose of this study was to evaluate whether the actions of clinically used estrogens on human aortic SMC biology are mediated by estrogen receptors. We examined the effects of various clinically used estrogens in the presence and absence of ICI 182,780, an estrogen receptor antagonist, on cultured human aortic SMC DNA synthesis ([H-3]thymidine incorporation), cellular proliferation (cell counting), cell migration (modified Boyden chamber), collagen synthesis ([H-3]proline incorporation), and mitogen-activated protein kinase activity. FCS-induced DNA synthesis, cell proliferation, collagen synthesis, platelet-derived growth factor-induced SMC migration, and mitogen-activated protein kinase activity were significantly inhibited by physiological (10(-9) mol/L) concentrations of 17 beta-estradiol and low concentrations (10(-8) to 10(-7) mol/L) of 17 beta-estradiol, estradiol valerate, estradiol cypionate, and estradiol benzoate but not by estrone, estriol, 17 alpha-estradiol, or estrone sulfate. The inhibitory effects of 17 beta-estradiol and other inhibitory estrogens were completely reversed by 100 mu mol/L ICI 182,780, and the rank-order potency of various estrogens to inhibit SMC biology matched their rank-order affinity for estrogen receptors, The inhibitory effects of estrogens on SMC biology are in part receptor-mediated, Because the cardioprotective effects of hormone replacement therapy are most likely mediated by modification of SMC biology, whether hormone replacement therapy protects a given postmenopausal woman against cardiovascular disease will depend partially on the affinity of the estrogen for estrogen receptors in vascular SMCs.