Evaluation of differential gene expression in blood vessels in response to estrogen and phytoestrogens

Estrogen is a reproductive steroid hormone that is protective to the cardiovascular system. Genistein and daidzein are isoflavones found in soybeans that have been shown to possess estrognic activity. Recent studies have indicated that these soy phytoestrogens modulate vascular function and blood pressure. However, the exact mechanism underlying the vascular protective effects of estrogens and phytoestrogens is still to be fully established. This dissertation project tested the hypothesis that the soy phytoestrogens, genistein and daidzein, mimic the effects of estrogen on gene expression in resistance blood vessels.; DNA microarrays were utilized to evaluate differential gene expression in the mesenteric arteries in response to a four-day estrogen and phytoestrogen treatment. The differentially expressed genes in the mesenteric arteries included biglycan, ECE-1, aldehyde dehydrogenase, α1 adrenergic receptor; FGF receptor activating protein-1, sodium chloride betaline/GABA transporter, Sprague Dawley protein kinase C receptor, inhibin, and megalin. Confirmation with multiplex semi-quantitative reverse-transcriptase polymerase chain reaction indicated that biglycan and endothelin-converting enzyme-1 (ECE-1) gene expression were decreased in response to estrogen and phytoestrogen. Addition of the pure steroidal antiestrogen, ICI 182,780, abolished the gene expression pattern that was observed in response to estrogen, genistein, and daizein treatments. These data suggest that estrogen and the phytoestrogens modulate biglycan and ECE-1 gene expression by an estrogen receptor mechanism. Tyrphostin-25 treatment had no effect on biglycan or ECE-1 gene expression suggesting that genistein effects were mediated by an estrogen receptor mechanism.; Similarly to the gene expression response in the mesenteric arteries, biglycan protein expression decreased in response to estrogen and phytoestrogen treatment. The biglycan protein was immunolocalized to the smooth muscle-rich media of the mesenteric arteries. Estrogen receptor-β protein levels increased significantly in response to estrogen treatment but not in response to genistein or daidzein treatment. Both estrogen receptor α and β isoforms were also localized in the media of the mesenteric artery.; In summary, the data from this project support the hypothesis that the phytoestrogens, genistein and daidzein, mimic the effects of estrogen on gene expression in the resistance blood vessels.