Project 455156

Background: Every 10 minutes a Canadian suffers a stroke. Strokes are caused by the build-up of fatty deposits (plaques) in the arteries of the neck, which can become 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. Aims: Research should focus on identifying the molecules that contribute to making plaques unstable in both women and men to better understand existing sex differences. Sex hormones are chemical messengers that not only play vital roles in sexual development, but also have wide-ranging effects in the body, including on arteries. Our project aims to investigate the role of sex hormones in the blood and plaque of women and men with stable versus unstable plaques and determine how that relates to sex differences at the cell and gene level of the blood/plaque. Methods: We will include women and men who underwent surgery to have plaques removed from their neck arteries. Plaques will be assessed under the microscope and labelled as stable or unstable. We will develop a sensitive method to measure sex hormones in the blood and plaque of these patients. Since blood and plaques are composed of various cell types, we will use a powerful new technique, called single-cell RNA sequencing, that will provide the genetic profile of individual cells present in the blood/plaque. These profiles will be compared between women and men with stable and unstable plaques and correlated with sex hormone levels. Impact: This study will help identify sex-specific markers that can predict the development of unstable plaques and new targets for therapy resulting in patient care tailored to both women and men. Ultimately, we could implement better clinical guidelines to prevent strokes and save lives!