Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Angiogenesis is a process of new vessels formation mediated by endothelial cells, which is essential during pregnancy to allow an adequate placental formation and blood supply to the growing baby. Till now, our understanding of angiogenesis mechanisms in pregnancy is very limited, particularly during placenta formation when impaired micro-vessels formation can lead to maternal stress and high blood pressure (or hypertension). This is relevant because one in ten pregnancies in the world have hypertensive disorders. They cause one in four preterm births and are responsible for the death of more than 70,000 mothers and 500,000 infants each year. In survivors, they can dramatically increase heart disease risks by causing heart and vessels changes evident in mothers and in their children as early as in fetal development. These numbers reflect the currently insufficient knowledge on causes of hypertensive pregnancies added by ineffective therapies to reduce maternal blood pressure, which could, collectively, enhance early interventions in high-risk pregnancies and the prevention of diseases. This research project will fill some of these gaps by studying new mechanisms and therapies tackling a maternal "anti-angiogenic" state in hypertensive pregnancy with an extended potential to prevent heart diseases in children. This proposal uses a translational (bench-to-clinic) approach by including experiments in mice and in human-derived placental units targeting new anti-angiogenic mechanisms identified by our group in hypertensive patients and in a genetic mice model of hypertensive pregnancy. Given that this mice model also triggers significant heart changes in babies, mainly in females, this approach has another great potential to identify sex-based mechanisms relevant in fetal heart development and diseases. This will significantly contribute to better understand the angiogenesis mechanisms driving hypertensive disorders in mother and children beyond pregnancy, which may accelerate new targeted and effective therapies to preventing cardiovascular diseases in mother and child.