Grant: Master's Award: Canada Graduate Scholarships

Pulmonary arterial hypertension (PAH) is a deadly cardiovascular disease that affects thousands of men and women across Canada. PAH results from excessive growth of the cells lining the arteries in the lungs and causes restriction and blockage of blood flow from the right side of the heart. This puts the heart under immense stress, and often leads to death from right heart failure. Currently, treatments for PAH aim to lessen symptoms instead of targeting the true cause of the disease. Consequently, 15% of patients die each year. The natural killer (NK) cells of the immune system identify and remove stressed, infected or cancerous cells in the body. In addition to this role in immune surveillance, NK cells are involved in the formation of blood vessels needed for the development of the placenta during pregnancy. This function of NK cells is not limited to placental development and can also occur in other areas of the body, impacting vascular remodelling in diseases such as cancer and PAH. In these cases, it is thought that NK cells obtain this specialized function inappropriately after exposure to transforming growth factor beta (TGFB), a protein that is expressed in the uterus during pregnancy. Our lab has shown that NK cells are reduced in number and have impaired functions in PAH patients. We have also shown an increase in TGFB in these patients. However, the exact mechanism behind the disease-associated vascular remodelling is unknown. This project aims to clarify these mechanisms by using animal models to investigate the influence of TGFB on PAH development. We expect that animals lacking sensitivity to TGFB in their NK cells will be protected from developing disease. We hope that our findings will help find a better treatment for PAH patients.