Grant: Project Grant

Cardiovascular diseases (CVDs) are the leading cause of death in the world. Sex differences exist in the burden of CVDs, and sex-specific factors, particularly pregnancy, contribute to these differences. For example, women who had a pregnancy complicated by preeclampsia are at higher risk of having a heart attack or stroke (the most common CVDs) later in life. Preeclampsia is a common complication of pregnancy and is a leading cause of sickness to the mother and her child. It is diagnosed by the onset of high blood pressure and impaired blood vessel function in the last half of pregnancy. Women who experience excessively high blood cholesterol levels during pregnancy are at increased risk for developing preeclampsia, and these high cholesterol levels are also a hallmark of many CVDs. Thus, to prevent maternal blood vessel problems in pregnancy, as well as CVDs later in life, it is essential to study the underlying mechanisms by which high blood cholesterol/preeclampsia impacts maternal vascular health during and after pregnancy. In this proposal, we will use an animal model of excessive amounts of blood cholesterol during pregnancy, which has similar characteristics to what is seen in women with preeclampsia. We will study why and how excessive amounts of blood cholesterol during pregnancy can lead to impaired blood vessel function in the mother, both during and after pregnancy. As these effects of high blood cholesterol are pregnancy-specific, we will also address the role that the placenta may play. In addition, we will evaluate the long-term effects of a (clinically relevant) intervention with cholesterol lowering drugs on blood vessel function in the mother later in life. The results of these studies will contribute to increasing our understanding of the mechanisms of CVDs in mothers who experienced (severe) complications during pregnancy, and to the development of a targeted therapeutic treatments to improve cardiovascular health in these women later in life.