(Hypertension. 1999;33:177-182.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Phytoestrogens Inhibit Growth and MAP Kinase Activity in Human Aortic Smooth Muscle Cells
From the Center for Clinical Pharmacology, Departments of Medicine (R.K.D., D.G.G., E.K.J.) and Pharmacology (E.K.J.), University of Pittsburgh Medical Center, Pittsburgh, Pa; and Clinic for Endocrinology, Department of Obstetrics and Gynecology, University Hospital Zurich, Switzerland (R.K.D., B.I., M.R., P.J.K.).
Correspondence to Dr Raghvendra K. Dubey, Department of Obstetrics and Gyaenocology, Clinic for Endocrinology, Frauenklinikstr 10, University Hospital Zurich, 8091 Zurich, Switzerland. E-mail dubey{at}med1.dept-med.pitt.edu
Abstract—Estrogens are known to induce cardioprotective effects by inhibiting smooth muscle cell (SMC) growth and neointima formation. However, the use of estrogens as cardioprotective agents is limited by carcinogenic effects in women and feminizing effects in men. If noncarcinogenic and nonfeminizing estrogenlike compounds, such as natural phytoestrogens, afford cardioprotection, this would provide a safe method for prevention of cardiovascular disease in both men and women. Therefore, we evaluated and compared in human aortic SMCs the effects of phytoestrogens (formononetin, genistein, biochanin A, daidzein, and equol) on 2.5% fetal calf serum–induced proliferation (3H-thymidine incorporation and cell number), collagen synthesis (3H-proline incorporation), and total protein synthesis (3H-leucine incorporation) and on PDGF-BB (25 ng/mL)–induced migration (modified Boydens chambers). Moreover, the effects of phytoestrogens on PDGF-BB (25 ng/mL)–induced mitogen-activated protein kinase (MAP kinase) activity in SMCs was also studied. Phytoestrogens inhibited proliferation, collagen and total protein synthesis, migration, and MAP kinase activity in a concentration-dependent manner and in the following order of potency: biochanin A>genistein>equol>daidzein>formononetin. In conclusion, our studies provide the first evidence that in human aortic SMCs phytoestrogens inhibit mitogen-induced proliferation, migration and extracellular matrix synthesis and inhibit/downregulate MAP kinase activity. Thus, phytoestrogens may confer protective effects on the cardiovascular system by inhibiting vascular remodeling and neointima formation and may be clinically useful as a safer substitute for feminizing estrogens in preventing cardiovascular disease in both women and men.
Key Words: estrogen • muscle, vascular, smooth • women, postmenopausal • cardiovascular disease • phytoestrogens • proliferation • migration
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