Alternative ways to treat pulmonary hypertension

The role of bromodomain-containing protein in vascular cell inflammation and proliferation in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is abnormally high blood pressure in the arteries carrying blood to the lungs, causing damage to the right side of the heart. Symptoms include breathlessness or tiredness. The condition can lead to death from heart failure within a few years. The predicted outcome of many patients with PAH is poor because there are very few treatments available. Cells lining the inner wall of blood vessels (endothelial cells) and cells making up the blood vessel walls (smooth muscle cells) from PAH patients respond differently to inflammation and divide and survive differently. Scientists believe that a process called ‘histone acetylation’ is important in controlling these processes but it has not been studied in PAH. The BHF has awarded a grant to Prof Ian Adcock and his team at Imperial College London to determine whether a protein that is known to affect histone acetylation, called Brd4, plays a role in PAH. They will use endothelial and smooth muscle cells taken from patients and an animal model of PAH to find out whether a drug that targets Brd4 can improve PAH. Histone acetylation occurs when a small chemical is added to the histone proteins around which DNA is tightly coiled, which can help to turn genes on and off. Changes to these histone proteins are called epigenetic changes. As well as revealing if Brd4 targets are a new way to treat PAH, this research may also determine if reversing the epigenetic ‘switches’ could be a new avenue for PAH research.