Grant: Team Grant: Transnational Cardiovascular Research Projects

Patients with pulmonary hypertension (PHT; high blood pressure in the lungs) have a dysfunction of the cells constituting the wall of their arteries in the lungs. These cells proliferate like cancer cells and create an obstruction of the vessels, making it difficult for the blood to go through. They also have evidence of inflammation in their blood, similar to patients suffering from infections. Finally, in patients with PHT several organs display the same abnormal way to produce energy (metabolism). PHT occurs more often in women than in men and it's an area of ongoing research. Women have 2 chromosome x, and one is normally inactivated to equal gene expression of men that have one X and one Y chromosome. In some diseases like cancer, the inactivated chromosome X is re-activated, resulting in increased expression of genes located on the chromosome X. We hypothesized that this phenomenon also occur in women with PHT. We will study the state of activation of the chromosome x in 30 women with PHT compared to 30 healthy control women, as well as in animal models. We will study the mechanisms responsible for chromosome X reactivation and test whether we can reverse it in cells in culture, lung slices and animal models, using specific inhibitors of factors influencing chromosome X reactivation.