Prolonging the life of coronary artery bypass grafts

Assessment of the efficacy of antifibrotic gene transfer as a means of suppressing neointima formation in venous arterial-interposition grafts

Dr Paul Kingston and his colleagues at the University of Manchester are looking for ways to prevent complications in people who have coronary artery bypass grafting surgery to treat coronary artery disease. The most common vein used in coronary artery bypass grafting is the saphenous vein, taken from the patient’s leg. However, within ten years almost half of saphenous vein grafts are blocked, often by a scar-like material called neointima. We need new ways to prevent vein grafts from failing, helping people to live longer without angina and surgery, improving their quality of life. Dr Kingston’s team has developed genetically-engineered viruses containing genes called fibromodulin and LAP- ß1. These viruses prevent scar-like material forming in segments of human vein graft in the lab. In this project, they will find out if these viruses can prevent scars forming in pigs undergoing coronary artery bypass grafting surgery. They will test if fibromodulin and LAP-ß1 work better than a gene called TIMP-3 at preventing scars in animals, as they believe they may prevent vein graft failure better than TIMP-3 in people. This research will determine whether these genetically-engineered viruses can prevent vein graft failure in animals, and may pinpoint which are most likely to be effective in people. It may pave the way for research to move these new treatments towards the clinic to benefit patients in the near future.