Grant: Operating Grant

Blood in a pregnant woman contains the oxygen and nutrients that allows her unborn baby to grow well. Blood from the mother flows to the uterus and placenta to nourish the unborn baby. If this blood flow is decreased, the growth of the baby is reduced leading to many complications just after birth. Their risk of heart disease when they become adults is also increased. When arteries are widened or relaxed, blood flow is increased. When narrowed or constricted, blood flow is reduced. The vessel lining normally acts as a partial barrier and controls the access of factors in the blood to the smooth muscle cells that cause constriction. In unhealthy pregnancies, the barrier becomes leaky. One factor that can affect the barrier is sphingosine 1-phosphate (S1P). This factor relaxes the blood vessel if it remains inside. However, it constricts the vessel if it leaks through the barrier to reach the muscle layer. This study looks at a novel role for S1P in controlling leakiness of blood vessels in the mother that control her blood pressure and also the ones that feed her baby. We will also look at the role of S1P in controlling relaxation compared to constriction in these vessels. We will study how inflammation can change these normal responses and cause high blood pressure in the mother and reduce blood flow to the baby. We propose that S1P will reduce leakiness and increase relaxation of arteries in normal pregnancies. On the other hand, in mothers with inflammation, we predict that S1P will leak through the vessel lining and cause the muscle layer to constrict. This will increase blood pressure in the mother and reduce blood flow to the baby. Our work will be done using a mouse model and we will also study human placental arteries from normal and abnormal pregnancies. Knowing what happens in normal pregnancy and during inflammation will help to develop methods to improve growth of the unborn baby and prevent high blood pressure in the mother.