Project 1: Estradiol and testosterone regulation of cardiac injury
Epidemiological studies demonstrate that women are less prone to ischemic heart disease than men. The mechanisms responsible for the differences in ischemic injury observed between men and women are not known although the current focus is on sex hormones, in particular estrogen and testosterone. A large number of studies have implicated estrogen-induced stimulation of a molecule known as nitric oxide synthase as providing protection against ischemic cardiac injury. The role of testosterone is unclear with reports of protection against ischemic injury and reports of testosterone promoting ischemic injury. The majority of the studies on estrogen and testosterone do not distinguish between effects caused by the cells lining the blood vessels of the heart, i.e. the endothelium, versus the actual cells of the heart known as the cardiac myocytes. Project 1 will test the hypothesis that the sex hormones estrogen and testosterone regulate the activity of the heart cells to produce nitric oxide synthase which subsequently affects the extent of ischemic injury. The molecular mechanism whereby estrogen limits ischemic injury and testosterone increases ischemic injury will also be explored.
Project 1 investigators: