The role of iron in pulmonary arterial hypertension

Iron homeostasis in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare but fatal disorder of high blood pressure in the arteries that supply the lungs, causing breathlessness and swelling of the feet or ankles. In PAH the arteries become narrowed, are less able to stretch, and the heart has to work harder to pump blood to the lungs. Eventually the heart begins to work less effectively, leading to heart failure or death. Although treatments are available that help relax and widen these vessels, they are not fully effective. Iron is thought to help fight some of the damaging effects that arise as a result of PAH. Scientists understand that iron plays an important part in the normal function of the circulatory system, playing a key role in transporting oxygen around the body via the bloodstream. Professor Martin Wilkins’ team from Imperial College London has recently identified that iron deficiency is common in patients with a particular form of PAH called ‘idiopathic’ PAH, and iron control may be disrupted in these patients too. The team are now investigating the idea that iron replacement could become a successful treatment for some PAH patients. The researchers will look at iron levels in patients at the Hammersmith Hospital in London, to see if they can confirm a link between iron deficiency and higher chance of death in patients with idiopathic PAH. Patients from the Hammersmith and other hospitals in Sheffield and Cambridge are also being enrolled to a study to investigate whether treatment with iron supplements can improve blood flow, exercise ability and quality of life. The patients will be monitored throughout and after treatment. Alongside this work, the researchers are comparing tissue samples from healthy individuals and people with PAH, to investigate the behaviour of proteins in the circulatory system that control iron activity. This work may reveal whether genetic errors help cause insufficient levels of iron in the arteries supplying the lung. Professor Wilkins’ team will also look at how iron levels affect the structure and function of the arteries supplying the lungs and the heart in rats and mice with PAH, and examine the effect of iron treatment on these animals. This thorough research programme is using a wide variety of scientific techniques in the laboratory and beyond to improve the outlook for patients.