(Hypertension. 1998;31:522.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
17ß-Estradiol, Its Metabolites, and Progesterone Inhibit Cardiac Fibroblast Growth
From Center for Clinical Pharmacology, Departments of Medicine (R.K.D., E.K.J.) and Pharmacology (E.K.J.), University of Pittsburgh Medical Center, Pittsburgh, PA, USA, and Clinic for Endocrinology, Department of Obstetrics and Gynecology, University Hospital Zurich, Zurich, Switzerland (R.K.D., P.J.K.).
Correspondence to Dr Raghvendra K. Dubey, Center Pharmacology. Department of Medicine, 623 Scaife Hall, 200 Lothrop Street, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. E-mail dubey{at}med1.dept-med.pitt.edu
Postmenopausal women (PMW) have increased incidence of cardiovascular disease, and estrogen substitution therapy has been shown to have cardioprotective effects. Since abnormal growth of cardiac fibroblasts (CFs) is associated with hypertension and myocardial infarction and estrogen inhibits vascular smooth muscle cell (SMC) growth, it is feasible that estrogen may attenuate cardiac remodeling by inhibiting CF growth, and this possibility was investigated by using cultured CFs. 17ß-Estradiol and progesterone, but not 17
-estradiol, estrone, or estriol, inhibited 2.5% FCS-induced proliferation (DNA synthesis and cell number) and collagen synthesis (3H-proline incorporation) in a concentration-dependent manner and to a similar extent in male and female CFs. Compared to 17ß-estradiol, its metabolites 2-hydroxyestradiol and 2-methoxyestradiol were more potent in inhibiting FCS-induced DNA synthesis, collagen synthesis, and cell proliferation. The inhibitory effects of 17ß-estradiol and its metabolites were enhanced in presence of progesterone and 4-hydroxytamoxifen (high-affinity estrogen receptor ligand). Moreover, like estrogens, the dietary phytoestrogens biochanin A and daidzein inhibited FCS-induced growth of CFs. In conclusion, 17ß-estradiol, its metabolites, and progesterone inhibit CF growth in a gender independent fashion. Moreover, hormone replacement therapy using 17ß-estradiol and progesterone may protect PMW against cardiovascular disease by inhibiting CF growth and cardiac remodeling; whereas estrogens that do not inhibit CF growth may be less effective in protecting PMW against cardiovascular disease. Finally, our studies provide evidence that phytoestrogens inhibit CF growth and may be clinically useful as a substitute for feminizing estrogens in preventing cardiovascular disease in both women and men.
Key Words: estrogen(s) • phytoestrogens • 17ß-estradiol • cardiac fibroblast • postmenopausal women • hormone replacement therapy • cardiovascular disease • proliferation • hypertrophy
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