Working out why pulmonary arterial hypertension is more common in women

Investigating oestrogen metabolism in pulmonary artery smooth muscle cells

Professor Margaret MacLean and her team at the University of Glasgow want to understand why women are more prone to get pulmonary arterial hypertension (PAH) than men. In PAH, cells lining the arteries in the lungs overgrow, causing narrowing and high blood pressure in these arteries, putting a strain on the heart, which has to pump blood through the narrow vessels. Current treatments relieve the symptoms but many people still die within a few years of heart failure. We don’t know why more women than men get PAH. A form of the hormone oestrogen, called oestradiol (or E2) may be involved, as it boosts the growth of lung artery smooth muscle cells. E2 can also be changed chemically (metabolised) into other molecules (metabolites) and these metabolites may then thicken lung artery walls by increasing the number of cells in the wall Professor MacLean has found that cells from PAH patients, especially cells from women, turn E2 into damaging metabolites. She thinks E2 metabolism may be controlled differently in men and women. In this project, Professor MacLean and her team will use a new experimental approach to detect and measure multiple metabolites based on their size. They will study lung artery muscle cells from male and female patients, and from patients with a hereditary form of PAH. This research will reveal whether differences in E2 metabolism between men and women with PAH explain why more women get the disease, and could help identify new treatments.