Oestrogen and oestrogen metabolites in pulmonary arterial hypertension

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Pulmonary Arterial Hypertension (PAH) is a disease where the blood vessels of the lungs thicken and close down. This puts strain on the right side of the heart which eventually fails. Survival is very poor and many more women than men get this disease. The sex hormone oestrogen (E2) can cause similar changes to the blood vessels and this may be due to them being broken down (metabolised) in the body to other more toxic chemicals. Many clinical trials are ongoing using drugs that interfere with the effects of E2. Using a novel assay we will measure E2 and its metabolites in the blood taken from patients with PAH and see how the change with disease severity, sex, age and obesity. We will also examine how the lungs themselves metabolise E2 in patients. We will analyse blood from patients in clinical trials for drugs that affect E2. We will to see how the drugs affect E2 and its metabolism and how this relates to the therapeutic effects of the drugs. We will examine lung blood vessel cells from patients with PAH and examine how E2 and its metabolites affect the way they grow and move. We will also study a rat model of PAH to determine how E2 metabolism changes during the development of the disease and is affected by the sex of the animal.