Prof Sarah George
University of Bristol
Heart attacks are usually caused by blockage of the coronary arteries supplying blood to the heart muscle. One of the treatments for blocked coronary arteries is heart bypass surgery using sections of vein from the patient’s leg to bypass the blockage. Unfortunately, these vein grafts suffer from unacceptably high failure rates, with approximately 50% failing within ten years. This means that many patients will go on to experience recurrent angina or heart attacks, and need further operations.
Vein graft failure is caused by increased activity of cells within the vein graft which causes thickening of the inner layer of the vein, leading to blockages. In this project, Professor George’s team developed and tested a new laboratory model to help understand why vein graft failure happens and test new treatments to prevent it.
The team identified a protein, called N-cadherin, that plays an important part in the binding of cells to one another. They showed that N-cadherin inhibits activity of the graft cells and reduces graft thickening, without harmful effects on the blood vessel wall. They also found that a very small part of N-cadherin had similar effects on the vein graft, so can act as a mimic for the full-length version.
So that the treatment can be targeted to the area of the vein graft, the team produced a biodegradable wrap to place around the graft. The wrap encased a new treatment which consisted of a type of ‘stem cell’ collected from the patient’s skin fat which was genetically altered in the lab to produce the N-cadherin mimic. Also, they packaged the skin cells in small biodegradable spheres to deliver the mimic in a prolonged, continuous way to the vein graft.
Further research is now needed to confirm that the mimic can be delivered so that it reduces over-activity of the cells within the vein graft and prevents thickening, without damaging the blood vessel wall. If successful, it could be used to prevent vein graft failure following heart bypass surgery, improving outcomes for patients and reducing the need for surgery to be repeated.