Piezo1 couples lipids and vascular function in the placenta

Preeclampsia is a pregnancy disorder characterized by high blood pressure. It is a leading cause for death of mothers and offspring in Europe and affects more than 5800 pregnancies in Austria per year. Even in later life both, mother and child, carry a higher burden for disease. If the situation during pregnancy becomes too threatening for mother and the unborn fetus, the only available therapy option is typically the delivery before term. The mechanisms causing preeclampsia are barely understood. However, it is known that the placenta, which is developed during pregnancy, plays the decisive role. As the connecting organ between the side of the mother (maternal) and the side of the fetus (fetal) it fulfills several important tasks. These include providing nutrients and oxygen to and removing waste products from the fetus as well as communicating with the immune system of the mother. In preeclampsia the placenta does not develop properly. Therefore, it does not get the required supply through the maternal blood and reacts with stress. This leads to the release of pro-inflammatory molecules from the placenta -including so called bioactive lipids- into the maternal circulation causing the preeclampsia symptoms. We also know that in preeclampsia the blood vessels of the placenta are abnormal. This is a problem because they play a key role for the exchange between the fetal and maternal circulation. Therefore, we want to better understand why the placental blood vessels develop differently and do not function properly in preeclampsia. To do so, our project, as the first study worldwide, investigates the role of the calcium channel Piezo1, whichs discovery was recently awarded with the Nobel Prize. It is located in the membrane of many cells in the body and can sense mechanical stimulation. Thereby it regulates different processes in the body, such as the diameter of blood vessels if the blood flow increases. Furthermore, its function can be changed through (bioactive) lipids. In this project we work with a team of international scientists to find out which role Piezo1 plays in placental blood vessels and how its function is affected in preeclampsia. Therefore, we investigate placentas from healthy and preeclamptic patients after they have given birth. Starting on cellular level, we examine where Piezo1 is located in the placenta, how its function is regulated as well as the influence of the bioactive lipids. As final part of the study we will investigate Piezo1 function by ex vivo perfusion a technique in which a part of the placenta and thereby the interplay of maternal and fetal circulation can be maintained after birth and investigated in the lab. All this will provide new insights into the role of Piezo1 in the placenta in preeclampsia and how its function is regulated. This knowledge will contribute to find new possibilities for therapies in the future.