9931101

pubmed:Citation

1 Pt 2

-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.

eng

IM

MEDLINE

0194-911X

Print

NLM

177-82

pubmed-meshheading:9931101-Adult, pubmed-meshheading:9931101-Animals, pubmed-meshheading:9931101-Aorta, Thoracic, pubmed-meshheading:9931101-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:9931101-Cattle, pubmed-meshheading:9931101-Cell Division, pubmed-meshheading:9931101-Cell Movement, pubmed-meshheading:9931101-Cells, Cultured, pubmed-meshheading:9931101-Chromans, pubmed-meshheading:9931101-Culture Media, pubmed-meshheading:9931101-DNA, pubmed-meshheading:9931101-Dose-Response Relationship, Drug, pubmed-meshheading:9931101-Equol, pubmed-meshheading:9931101-Estrogens, Non-Steroidal, pubmed-meshheading:9931101-Female, pubmed-meshheading:9931101-Genistein, pubmed-meshheading:9931101-Humans, pubmed-meshheading:9931101-Isoflavones, pubmed-meshheading:9931101-Kinetics, pubmed-meshheading:9931101-Male, pubmed-meshheading:9931101-Muscle, Smooth, Vascular, pubmed-meshheading:9931101-Phytoestrogens, pubmed-meshheading:9931101-Plant Preparations, pubmed-meshheading:9931101-Protein Biosynthesis

Phytoestrogens inhibit growth and MAP kinase activity in human aortic smooth muscle cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't