Grant: CIHR Fellowship

Cardiovascular diseases such as heart attacks and stroke are the leading causes of illness and death in Canada. These diseases are caused by the narrowing of the lumen of blood vessels in part due to build up of fibrofatty plaques on the vessel walls. The cells lining the blood vessel lumen, called endothelial cells, play key role in this process, which is known as atherosclerosis. Estrogen, a key female sex hormone, appears to protect against cardiovascular disease in premenopausal women compared to men in the same age range. However, the mechanisms by which such protection is exerted remains unclear. Nitric oxide is a molecule generated in endothelial cells in response to estrogen. Nitric oxide can be generated by different isoforms of the enzyme nitric oxide synthase. I have recently characterized a novel isoform of nitric oxide synthase in the nucleus of endothelial cells. This enzyme, called neuronal nitric oxide synthase (nNOS) has been traditionally described only in nerves where it can be a target of estrogen action. In my research project, I will examine the role of estrogen on nitric oxide generation in vascular endothelial cells involving this novel enzyme. Specifically, I will look into the role of this novel nitric oxide producing enzyme on changes in the endothelium that predispose to developing atherosclerosis. This work will lead to a better understanding of the role of estrogen on prevention of cardiovascular diseases such as heart attacks and stroke and may lead to the development of novel therapeutic opportunities.