Looking for ways to repair a broken heart

Sulfatases: novel targets for enhancing regeneration by epicardium-derived cells

Dr Nicola Smart and colleagues at the University of Oxford are looking for new ways to repair damaged heart muscle cells and boost heart repair after a heart attack, to prevent heart failure. Dr Smart discovered that in mice, cells that form the outer layer of the heart, known as epicardial cells, can be stimulated to move into the damaged area of the heart after a heart attack and generate new muscle and blood vessels. But this process is not very efficient - very few epicardial cells go through the significant change needed to contribute to new tissue. This important change is called epithelial mesenchymal transition (EMT). Fibroblast growth factor proteins, called FGFs, drive EMT in embryonic development and the processes involved when zebrafish regenerate their heart after injury. Dr Smart has discovered that enzymes called sulfatases control the sensitivity of epicardial cells to respond to FGF, and that blocking sulfatases in cells increases the number that undergo EMT. In this project, Dr Smart wants to better understand how sulfatases affect EMT and control the movement of epicardial cells. She wants to test a series of small molecules to see if they could become drugs to block sulfatase actions, helping outer layer cells to move and promote muscle repair in the damaged heart. If successful, this research could reveal a new way to treat heart failure by encouraging the heart to make new muscle and vessels that restore the blood supply.