Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain

During their reproductive years women produce significant levels of estrogens, predominantly in the form of estradiol, that are thought to play an important role in cardioprotection. Mechanisms underlying this action include both estrogen-mediated changes in gene expression, and post-transcriptional activation of protein signaling cascades in the heart and in neural centers controlling cardiovascular function, in particular, in the brainstem. There, specific neurons, especially those of the bulbar region play an important role in the neuronal control of the cardiovascular system because they control the outflow of sympathetic activity and para-sympathetic activity as well as the reception of chemical and mechanical signals. In the present review, we discuss how estrogens exert their cardioprotective effect in part by modulating the actions of internally generated products of cellular oxidation such as reactive oxygen species (ROS) in brain stem neurons. The significance of this review is in integrating the literature of oxidative damage in the brain with the literature of neuroprotection by estrogen in order to better understand both the benefits and limitations of using this hormone to prevent cardiovascular disease.