IMPHLeXIONS

Pulmonary arterial hypertension is a rare, but progressive fatal disease of the pulmonary circulation affecting primarily females. The INPHLeXIONS project consortium will investigate the underlying molecular mechanisms that lead to observed gender bias in this disease. Research groups from Austria, Germany and Canada will apply newly developed technologies to characterize aberrant inactivation of X chromosome-linked genes involved in inflammatory and metabolic processes. Gained insights will be used to develop and validate novel therapeutic options for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare but serious disease affecting the lungs, and it affects women much more often than men. The reasons for this difference aren't fully understood, so our project looked at whether certain genetic factors might increase the risk for women. Unlike men, who have one X chromosome, women have two. Usually, only one X chromosome is active in each cell, so that men and women get a similar amount of information from this chromosome. However, in some female cells, certain genes remain active on both X chromosomes; these are called "escapees." To study this, we looked at cells from women with and without PAH to see if women with PAH had more of these "escapee" genes, which could increase their risk. Interestingly, we found that women with PAH did not have more escapees than healthy women. However, some of the most common escapee genes we found, play important roles in the body and could influence how cells behave in ways that differ between men and women. This might mean that women naturally carry a slight genetic tendency to develop PAH, even if other factors are needed to trigger the disease.