Chronic graft loss: dealing with the vascular alterations in solid organ transplantation

Abstract

CURRENT transplantation research has focused on the late loss of graft function and specifically on the vascular alterations, or graft vessel disease (GVD), which contribute to this clinical problem. Mechanisms involved in the multi-factorial GVD process are poorly understood and with most of the available models established in rodents, there are concerns about the predictivity of the mechanisms involved for human grafts. The situation is further complicated by the lack of a proven pharmacologic “gold standard,” to validate the animal models. It is clear that GVD involves both immunological and non-immunological or vascular components, with evidence suggesting that key events at or soon after transplantation have a significant effect upon long-term graft survival. This brief review focuses on the early cascade of events in relation to chronic graft function, concentrating in particular on the involvement of vessel wall cells in the disease process. We conclude that animal GVD models need to include a physiological assessment of graft function, if we are to make progress in the understanding and treatment of the chronic rejection process in man.