Estrogen-based drug therapy in cardiovascular diseases has been difficult because it has not been possible to separate the wanted vasculoprotective effect from the unwanted effects of the hormone to the reproductive system. Here, we demonstrate that, after endothelial denudation of rat carotid artery, the mRNA of the classical estrogen receptor (ERα) is constitutively expressed at a low level whereas the expression of the novel ERβ mRNA increases >40-fold. Under in situ hybridization and immunohistochemistry, ERβ mRNA and protein colocalize with the smooth muscle cells in the media and neointima. Treatment of ovariectomized female rats with the isoflavone phytoestrogen genistein, which shows 20-fold higher binding affinity to ERβ than to ERα, or with 17β-estradiol, which does not differentiate between the two receptors, provides similar dose-dependent vasculoprotective effect in rat carotid injury model. In addition in concentrations <10 μM, both ligands are equally inhibitory to the replication and migration of smooth muscle cells in vitro. However, only treatment with 17β-estradiol, but not with genistein, is accompanied with a dose-dependent uterotrophic effect. The results suggest that preferential targeting to ERβ will provide vasculoprotective estrogen analogs devoid of effects to the reproductive system.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jun 8 1999|
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