How is oestrogen linked to pulmonary arterial hypertension?

Sex and the development of pulmonary arterial hypertension (renewal)

Professor Margaret MacLean and colleagues at the University of Glasgow are studying why more women than men develop pulmonary arterial hypertension (PAH), but men die more quickly. In PAH, the pulmonary arteries (arteries of the lungs) thicken and narrow and blood pressure rises within the vessels. Blood cells can no longer pick up sufficient oxygen from the lungs, and the right side of the heart fails. We need to understand how this happens and why the outcome for men is worse. Professor MacLean has discovered that the female sex hormone oestrogen has a key role in the development of PAH. She has shown that a chamber of the heart, the right ventricle, makes oestrogen, and that heart oestrogen production may be higher in women than men. Also genes in the cells of the right ventricle of men and women respond differently to the higher pulmonary pressures found in PAH. In this project, Professor MacLean will study oestrogen’s role in PAH in more detail. People with PAH can become obese because it’s difficult for them to exercise. Oestrogen levels are raised in obesity, and Professor MacLean will explore whether obesity also contributes to PAH. Certain chemical signals in lung artery cells and right heart cells can cause PAH and the team will examine how oestrogens and body weight affect these signals in both males and females. They will study the effects of oestrogens and signalling pathways in cells from the right heart and artery cells from animal models of PAH as well as patients. Last, they will analyse measurements taken from a large study of people with PAH to find out how body weight and sex affects the development of PAH in men and women. This research will give clues to why PAH, as well as other heart and circulatory diseases, develop differently in men and women, and may identify new drugs to treat PAH.