A novel mechanism of caveolar protein regulation with therapeutic implications for pulmonary hypertension

Dr Bubb is currently investigating unknown causes and potential treatment options for pulmonary arterial hypertension (high blood pressure in the arteries in the lungs). This disease has a 100% mortality rate, with up to 50% of patients dying within 5 years of diagnosis.

It is a rare disease, but nevertheless is devastating for those who suffer from it. The patient’s quality of life is poor, as they suffer from shortness of breath, dizziness, fatigue and chest pain.

This is due to the rise in blood pressure in the lung circulation which is caused by changes in the cells that line the pulmonary arteries. These changes can cause the walls of the arteries to become stiff and thicken. The blood vessels may also become inflamed and tight.

These changes in the pulmonary arteries can reduce or block blood flow through the blood vessels. This makes it harder for blood to flow, raising the blood pressure in the pulmonary arteries. As a consequence of this increased pressure the blood can build up behind the lungs, in the right side of the heart. This can result in the right side of the heart having to pump harder to move the blood and it achieves this at first by the heart muscle growing larger and the chamber increasing. However, eventually the right heart will fail due to the extra load and this is what causes death in most patients.

Dr Bubb’s group has been working on a protein called FXYD1 for many years, and have shown the role that this protein has in protecting the heart from damage from free radicals.

She has been investigating this protein in the blood vessels and found that when it is absent the blood vessels have excessive free radical production and lose their ability to fully relax. Therefore, she is proposing that this protein may be important in the pulmonary vasculature (lung blood vessels) and could be dysfunctional in patients with pulmonary hypertension. She is investigating this using a variety of methods, in both cells and vascular tissue.