Looking for ways to prevent scars forming in heart muscle

Adenosine A2A receptors in myocardial fibrosis

Professor Houman Ashrafian at the University of Oxford is studying myocardial fibrosis – this is when scars form in the heart muscle without an obvious injury. It occurs in many heart diseases, including the inherited heart muscle condition, hypertrophic cardiomyopathy, and aortic valve stenosis. People with myocardial fibrosis have more severe disease because the scar tissue prevents the heart muscle from contracting and relaxing properly. Within the heart, cells called fibroblasts are responsible for producing scar tissue. They release a molecule called adenosine when the heart becomes stressed, and proteins on the cell surface that bind adenosine called A2A receptors (A2A-Rs) become activated and help to form the scar. Professor Ashrafian and his team have found that genetically removing A2A-Rs significantly reduces scar formation in mice with some heart diseases. He has also found that A2A-R activation in fibroblasts in the lab causes them to make more scar tissue. In this project, the researchers will investigate why these receptors become activated. They will try to quieten adenosine signalling in mice with heart disease to find out if this can stop scars forming.