Grant: Travel Awards - Institute Community Support

Having high amounts of cholesterol, a waxy, fat-like substance, in your blood is a major risk factor for the development of cardiovascular disease. However, during pregnancy having higher amounts of cholesterol in your blood is normal and needed for the development of the fetus. In some pregnant women, cholesterol levels increase too much, and this can result in blood vessel problems, leading to the development of pregnancy complications, such as preeclampsia. When pregnant women have preeclampsia, they have high blood pressure and damage to their blood vessels. There is currently no cure for preeclampsia. To prevent preeclampsia, it is essential to study the underlying mechanisms by which excessive amounts of cholesterol during pregnancy impact the vascular health of the mother. In this project, we used a rat model of high cholesterol during pregnancy and looked at various indicators of blood vessel function. Briefly, pregnant rats were fed a control or a high cholesterol diet during pregnancy. The rats that were fed the high cholesterol diet developed the same problems as women with preeclampsia. The rats on the control diet are our control group. We found that very high amounts of cholesterol during pregnancy leads to blood vessel dysfunction in uterine arteries (the blood vessels that supply the uterus and placenta), and we showed that inhibition of a membrane receptor called Toll-like receptor 4 improved blood vessel function. These studies increased our understanding of the mechanisms leading to blood vessel problems in mothers who have complicated pregnancies. In addition, our findings may contribute to the development of a potential targeted therapeutic to improve blood vessel health in women throughout their life.