Grant: Project Grant - PA: Sex and Gender in Health Research (Bridge funding)

Background: Every 10 minutes a Canadian suffers a stroke. Strokes are caused by the build-up of fatty deposits (atherosclerotic plaques) in the neck arteries, which can become dangerous (unstable), break-off, and block blood flow to the brain. While men develop unstable plaques more often than women, women have a greater chance of dying after a stroke. It remains unclear why this is the case. Currently, doctors take a "one size fits all" approach to managing strokes, leading women to be underdiagnosed and undertreated. Sex hormones are chemical messengers that are of interest to study in the context of plaque instability. Sex hormones have wide-ranging effects on cells present in the plaque, such as specialized muscle cells. These cells have the ability to change their function and influence the stability of the plaque. Aims: Our project will focus on identifying the mechanisms that contribute to making a plaque unstable in men and in women. Specifically, we will 1) identify the sex hormone profiles in the blood and plaque of men and women with stable vs unstable plaques, and 2) investigate how sex hormones change the function of these specialized muscle cells in the plaque. Methods: We will include men and women who underwent surgery to have plaques removed from their neck arteries. Plaques are assessed under the microscope and labelled as stable or unstable. Using our newly developed methods, we will measure sex hormones in the blood and in the plaque of these patients. Specialized muscle cells will be directly isolated from the plaque and their make-up and function will be assessed before and after treatment with sex hormones. Impact: This study will help identify new targets for therapy, tailored to men and women, that could promote the stabilization of a plaque. Ultimately, we could implement better clinical guidelines, prevent strokes, and save many lives!