Estrogen is a fascinating hormone with seemingly paradoxical effects in the cardiovascular system. On the one hand, estrogen appears to be protective to the cardiovascular system of pre-menopausal women. Prior to the menopause have a lower incidence of cardiovascular disease than men. After the menopause, the incidence increases rapidly to reach and even exceed that of men. It has been widely assumed, form anecdotal evidence, as ell as several early studies, that replacement of estrogen would return the cardiovascular system of the post-menopausal woman to its pre-menopausal protected state. However, the early data from the Women's Health Initiative does not support the assumption; rather, these data suggest an increase in cardiovascular events in the first two years of hormone replacement therapy with estrogen. Estrogen remains the most likely cardiovascular protective factor for pre-menopausal women. Thus we propose that the failure to observe a protective effect of estrogen on cardiovascular function is the result of administering an estrogen that is an incomplete agonist in cardiovascular tissues, or that is administered in inappropriate mode. This project is designed to test the hypothesis that the dichotomous effects of estrogen on the cardiovascular system are due to differential Gene expression responses to different estrogen formulations and modes of administration.
Two specific aims have been developed to test this hypothesis.
Specific aim #1 : To develop a profile of genes expressed in response to estradiol 17beta in vascular tissues and to examine the effect of estrogen formulation on the vascular reactivity of the mesenteric arteries.
| Mark-Kappeler, Connie J; Martin, Douglas S; Eyster, Kathleen M (2011) Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries. Vascul Pharmacol 55:42-9 |
| Eyster, Kathleen M; Mark, Connie J; Gayle, Richard et al. (2007) The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries. Vascul Pharmacol 47:238-47 |
| Mark, Connie J; Tatchum-Talom, Rabelais; Martin, Douglas S et al. (2007) Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed. Am J Physiol Regul Integr Comp Physiol 293:R1969-75 |
| Rodrigo, Manoj C; Martin, Douglas S; Eyster, Kathleen M (2003) Vascular ECE-1 mRNA expression decreases in response to estrogens. Life Sci 73:2973-83 |
| Rodrigo, Manoj C; Martin, Douglas S; Eyster, Kathleen M (2003) Estrogen decreases biglycan mRNA expression in resistance blood vessels. Am J Physiol Regul Integr Comp Physiol 285:R754-61 |
| Rodrigo, Manoj C; Martin, Douglas S; Redetzke, Rebecca A et al. (2002) A method for the extraction of high-quality RNA and protein from single small samples of arteries and veins preserved in RNAlater. J Pharmacol Toxicol Methods 47:87-92 |
