EXPOSURE OF VASCULAR ALLOGRAFTS TO INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) INCREASES VASCULAR EXPRESSION OF IGF-I LIGAND AND RECEPTOR PROTEIN AND ACCELERATES ARTERIOSCLEROSIS IN RATS

Background. Accelerated arteriosclerosis limits the survival of transp lanted hearts. We hypothesized that insulin-like growth factor-I (IGF- I) is crucial in accelerating transplant arteriosclerosis. Recently, w e reported that exposure to IGF-I prior to transplantation accelerates transplant arteriosclerosis in the rat aorta allograft model. Here, w e studied the mechanism whereby IGF-I exposure accelerates transplant arteriosclerosis. Methods. The abdominal aorta was harvested from male Brown Norway rats and exposed to 0, 200, or 500 ng/ml of IGF-I at 37 degrees C for 30 min prior to transplantation to the abdominal positio n of male Lewis rats. The allografts were harvested 14 days later and processed for immunohistochemical staining for alpha-actin, growth fac tors (IGF-I, IGF-I receptor, platelet-derived growth factor-BB, and ba sic fibroblast growth factor), and immunological markers (major histoc ompatibility complex class II antigen, macrophage, and CD4- and CD8-po sitive T cells). Results. By 14 days, the ex vivo IGF-I donor aorta tr eatment with IGF-I increased in a concentration dependent manner the e xpression of IGF-I and IGF-I receptor in both the intima and the adven titia. In contrast, the expression of platelet-derived growth factor-B B was decreased in a concentration-dependent manner in the intima whil e basic fibroblast growth factor remained unchanged. The cell-mediated immune response was not affected by IGF-I at 14 days after transplant ation, which suggests that the immune events associated with accelerat ion of transplant arteriosclerosis may occur at an earlier time. Concl usion. Acceleration of transplant arteriosclerosis by exposure to IGF- I is associated with increased IGF-I ligand and receptor expression in the allograft vascular wall. These data further suggest that IGF-I ma y be a major factor in mediating graft arteriosclerosis.