Estrogen affects cardiac function in health and disease: cellular mechanisms and novel treatment strategies

Pre-menopausal women are less likely to suffer from heart disease than are men, but this advantage disappears with age. This suggests that sex hormones such as estrogen influence heart disease. Even so, we know very little about the effects of estrogen on the heart, in part because most laboratory studies still use only male animals. Our group has explored the effects of estrogen on heart function in male and female mice. We discovered that calcium levels inside individual heart cells are lower in cells from young adult females compared to males. To mimic menopausal changes we removed the ovaries from some female mice, which reduces their estrogen levels. This caused the calcium levels in their heart cells to rise dramatically. We saw a similar increase in calcium levels in cells from very old female mice. This showed us that low estrogen states disrupt the ability of heart cells regulate internal calcium levels. Our findings are important, because some calcium is needed for the heart to contract, but the balance needs to be right. Too much (or too little) calcium in heart cells can lead to heart disease. There is still a great deal more to know about how estrogen affects the heart. We plan to investigate the mechanisms by which estrogen influences calcium regulation in heart cells. We also want to treat young and old animals with a new drug called G-1. This drug mimics the beneficial effects of estrogen, without harmful side effects on breast and ovary tissue. We plan to find out whether treatment with this drug can improve heart function in young and older hearts under disease conditions. This research project will help us understand the links between estrogen, aging and heart disease. This study is an important step in identifying and developing new therapies for the treatment of heart disease in older adults.