Investigating how very high cholesterol levels in the blood leads to pregnancy complications
Having high cholesterol levels is a risk factor for the development of cardiovascular disease, the leading cause of death worldwide. However, in pregnancy, having high cholesterol levels is a normal process essential for growth and development of the fetus. In contrast, having excessively high cholesterol levels during pregnancy increases the risk of complications such as preeclampsia. When pregnant individuals develop preeclampsia, both the individual and fetus become very sick. Currently, the only cure for preeclampsia is delivery of the placenta, thus the placenta is the key organ that may also be impacted by excessively high cholesterol levels. The placenta is an entirely new organ grown specifically during pregnancy and functions to provide oxygen and nutrients to the fetus. In previous studies, we demonstrated that excessively high cholesterol levels during pregnancy impairs uterine artery (the artery that supplies blood to both the uterus and placenta) and placental function via activation of a membrane receptor called toll like receptor 4 (TLR4). In this study, we aim to understand if inhibiting TLR4 in pregnancies with excessively high levels of cholesterol can improve maternal blood vessel and placental function. To do this, we will feed pregnant rats a standard diet or a high cholesterol diet. Rats will then be treated with or without a TLR4 inhibitor. At the end of pregnancy, we will assess blood pressure, blood vessel function and placenta biology. This study will help us understand how excessively high cholesterol levels during pregnancy impacts pregnancy outcomes and investigates a potential therapeutic approach that may improve pregnancy outcomes.