Cytochrome p450 2C Inhibition in Peri-transplant Ischemic Injury and Transplant Vascular Disease

Transplant vascular disease (TVD), characterized by a thickening of the arteries (arteriosclerosis), is the primary cause of chronic heart transplant rejection. TVD can be detected in up to 75 per cent of transplant recipients within only one year of transplantation. One factor that causes TVD is oxidative stress which occurs during the process of transplantation when blood flow is stopped in the donor heart prior to transplantation (ischemia), and then re-established in the recipient (reperfusion). This stress not only damages the heart but also makes it more susceptible to attack by the recipient’s immune system leading to chronic rejection. Previous research has suggested that an enzyme (CYP2C) is involved in triggering oxidative stress and heart damage during reperfusion. Arwen Hunter is investigating the process and mechanisms by which CYP2C causes cardiovascular damage. She will also investigate whether inhibition of CYP2C can suppress the amount of damage that occurs during transplantation and whether suppression of this damage can reduce chronic rejection later on. Results from these studies may lead to novel therapeutic strategies to alleviate chronic heart transplant rejection.