Grant: Operating Grant

Pulmonary arterial hypertension (PAH) is characterized by the progressive increase in pulmonary artery pressure and right heart failure. PAH predominantly affects young people between 20-60 years of age. The progressive obstruction of pulmonary vessels is related to the intense proliferation of cells in the walls of pulmonary arteries. We previously demonstrated that the proliferation of these cells is related to a reduction of microRNA-204. MicroRNA are molecules that regulate the effects of genes. However, the mechanisms by which miR-204 reduction promotes cells' proliferation remain unknown. Moreover, there is currently no explanation why pulmonary arteries of these patients get stiffer and tend to calcify. The proposed experiments will demonstrate that RUNX2, a factor that is activated by the reduction of microRNA-204, is central to PAH progression as it promotes cells proliferation and calcification. Through several experiments in humans and rats, the current proposal will not only demonstrate the importance of RUNX2 in PAH progression and severity, but will also open the door to new avenues of investigation and potentially to future therapies in PAH.