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Current Research Projects

early Prediction of preeclampsia Using arteriaL Stiffness in high-risk prEgnancies; a multinational study (PULSE)

Preeclampsia, a condition characterized by high blood pressure and multiple organ impairment, affects 5-8% of pregnancies and leads to serious complications for both mother and baby. Unfortunately, there is currently no useful clinical tool for its early prediction. The stages of preeclampsia initiate early in the first trimester, but clinical symptoms appear only in the second half of pregnancy. Thus, there is a window of opportunity to predict preeclampsia early in pregnancy. Previous tools that have been proposed have been shown to inadequately predict preeclampsia. On the other hand, it has been increasingly realized that malfunction of the mother’s arteries is associated with progression towards preeclampsia. Indeed, we have previously shown in a small group of pregnant women that this mal function may be detected, in the first trimester, as hardened arteries. The evaluation of arterial hardening can be performed safely and non-invasively, and is thus a promising tool for early preeclampsia prediction. The present study aims to determine in a larger population whether the assessment of arterial hardening can be used to predict preeclampsia. To do so, we will recruit pregnant women at high risk for preeclampsia from 8 obstetrical centers across North America and Europe. We will measure the hardening of the arteries in the first trimester and compare its predictive performance for preeclampsia to that of known clinical risk factors as well as alternative tools (e.g. blood tests, ultrasound). We will also perform the same assessments in the second trimester to determine whether preeclampsia risk prediction could be improved. Effective prediction of preeclampsia would identify pregnant women who would benefit most from preventive measures in a timely manner. Moreover, it will allow for the concentration of limited health care resources towards those women who are truly at high-risk, and help in the long-term to accelerate the development of new preventive treatments.

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Adiponectin Receptor paThway as a key playEr in carotid atheroscleRotic plaque instabilitY: what has sex got to do with it? (ARTERY)

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 as they have wide-ranging effects on arteries. Our project will focus on identifying the sex-specific mechanisms that contribute to making a plaque unstable in women and in men. Specifically, we will investigate the role of sex hormones in the blood and plaque of women and men with stable vs unstable plaques and determine how that relates to sex differences at the cellular and gene level of the blood and plaque.

Methods: We will include women and men 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 plaque of these patients. 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 women and to men. Ultimately, we could implement better clinical guidelines, prevent strokes, and save many lives!

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