Project 452729

Pulmonary arterial hypertension (PAH) is a lethal disease affecting the vessels in the lung and for which there is no cure. One of the reasons explaining the absence of treatment is that the mechanisms leading to the development of the disease are multifactorial and unclear. Moreover, the diagnosis of PAH requires invasive procedures, as there are currently no blood tests to diagnose PAH. The way that our genes express themselves governs virtually all the functions in our organism. DNA methylation is a chemical modification of a gene that disrupts its expression. These gene modifications can be transmitted to the offspring. Increased DNA methylation has been associated with multiple diseases (such as cancer and cardiovascular diseases), as well as a higher disease burden and death. The contribution of DNA methylation in the development and progression of PAH remains unknown. In this project, we aim to increase the knowledge on the mechanisms leading to PAH by evaluating if increased methylation has a role in the development and progression of the disease. We also wish to demonstrate that DNA methylation taken from the blood can be used as a test to diagnose PAH. We will also assess if DNA methylation abnormalities, which can be inherited, can help explain and identify familial cases of PAH. Finally, our study will evaluate if targeting DNA methylation would be an interesting therapeutic option to explore treatment of PAH.