Grant: Project Grant

Pre-eclampsia is a severe pregnancy complication that starts after 20 weeks of pregnancy, causing high blood pressure and damage to organs like the liver and kidneys. It affects 1 in 10 pregnancies and is a leading cause of death for mothers and babies worldwide. The only way to manage pre-eclampsia is by delivering the baby, as we do not have effective treatments to control the condition. Pre-eclampsia is linked to poorly developed placentas although we do not fully understand why and how this happens. Traditionally, scientists thought that issues with the placenta were caused by a dysfunction of its main cells, called trophoblasts. However, our team found evidence that the mother's endothelial cells, which line blood vessels in the uterus, also play a crucial role. We discovered that a protein called Thrombospondin-1 (THBS1) can disrupt vessels remodeling and stop new blood vessels from forming in the placenta. THBS1 activates another protein called TGF-beta, which seems to push endothelial cells to change in ways that block new blood vessel development and increase tissue stiffness. Our research team will investigate if in preeclampsia, blocking THBS1 in the mother's endothelial cells inhibits TGF-beta activation. This could cause the cells to change in ways to facilitate placental vessels remodeling and the formation of new blood vessels, preventing pre-eclampsia. First, we aim to understand how THBS1 and TGF-beta block blood vessel remodeling and growth in placentas. Second, we aim to study whether THBS1 plays a role on placental endothelial cells and trophoblasts communication to regulate placental vessels remodeling. Then, we will test treatments using a molecule called LSKL, which blocks TGF-beta activation by THBS1, assessing if it can improve placental blood vessel remodeling and growth in mice with preeclampsia. This project aims to uncover new ways preeclampsia develops, leading to potential new treatments to improve overall pregnancy outcomes.