Funding outcome

Preeclampsia (PE) is a pregnancy complication in which the mother presents with high blood pressure and organ damage during pregnancy. It is a significant cause of sickness and death for mothers and children worldwide. Additionally, women who have had PE and their children have an increased risk of developing cardiovascular diseases later in life. Unfortunately, we still do not know what causes PE and how it evolves. A protein of the immune system called Toll-like receptor 4 (TLR4) has been implicated in the development of cardiovascular diseases. When TLR4 is activated, it increases oxidative stress and inflammation, which harm blood vessels. However, we do not know if TLR4 is also responsible for problems in the mother's blood vessels during and after PE. We believe that PE is associated with increased TLR4 activation in the mother, which continues after the delivery of the fetus and impairs the cardiovascular system of these women. We will use an established rat model of PE. Briefly, pregnant rats will be fed a standard chow (uncomplicated pregnancy) or high-cholesterol diet (which causes experimental PE). We will treat a subset of rats with an antibody that binds to TLR4 and prevents its activation and assess whether this improves blood vessel function and pregnancy outcomes. We will also assess the long-term effects of PE by evaluating blood vessel function at one, 3, and 6 months postpartum (equivalent to ~3, 10, and 20 years after delivery in humans). This project will increase our understanding of PE, and consequently, our ability to design effective treatments against this disorder.