Do epigenetic clues hold the key to treating pulmonary hypertension?

The role of H3K27 methylation in vascular endothelial cell proliferation and function: Implications for pulmonary arterial hypertension

People with pulmonary arterial hypertension (PAH) have high blood pressure in their lungs. This causes a thickening of the lung’s blood vessel walls, which increases resistance to the blood flow but also puts a strain on the right side of the heart: the side that pumps blood to the lungs. There is no cure for PAH and current treatments use vasodilator drugs to open up blood vessels. Whilst this can help reduce the symptoms, these treatments do not address the problem of thickened vessel walls, and people with PAH still die from heart failure. Dr Wort and his team have been studying the lungs of people with PAH and found that a specific change to DNA structure (known as an epigenetic change) was seen less frequently in their blood vessels. They also found changes in the levels of the molecule that causes this alteration, JMJD3. This is the first evidences that these changes could be responsible for the vessel thickening seen in the lungs of people with PAH. In this project, they will measure amounts of this epigenetic change and levels of JMJD3 in blood vessel cells from the lungs of people with PAH and healthy controls. They will also test the effect of a new drug blocking JMJD3 on blood vessel cells isolated from people with PAH and on the thickening of the blood vessels in rats with pulmonary hypertension. If successful, this project might provide a new drug that could be a potential new treatment for PAH.