Abstract:
BACKGROUND:Accelerated arteriosclerosis limits the survival of transplanted hearts. We hypothesized that insulin-like growth factor-I (IGF-I) is crucial in accelerating transplant arteriosclerosis. Recently, we reported that exposure to IGF-I prior to transplantation accelerates transplant arteriosclerosis in the rat aorta allograft model. Here, we 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 position of male Lewis rats. The allografts were harvested 14 days later and processed for immunohistochemical staining for alpha-actin, growth factors (IGF-I, IGF-I receptor, platelet-derived growth factor-BB, and basic fibroblast growth factor), and immunological markers (major histocompatibility complex class II antigen, macrophage, and CD4- and CD8-positive T cells). RESULTS:By 14 days, the ex vivo IGF-I donor aorta treatment with IGF-I increased in a concentration-dependent manner the expression of IGF-I and IGF-I receptor in both the intima and the adventitia. In contrast, the expression of platelet-derived growth factor-BB was decreased in a concentration-dependent manner in the intima while basic fibroblast growth factor remained unchanged. The cell-mediated immune response was not affected by IGF-I at 14 days after transplantation, which suggests that the immune events associated with acceleration of transplant arteriosclerosis may occur at an earlier time. CONCLUSION: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 may be a major factor in mediating graft arteriosclerosis.
journal_name
Transplantationjournal_title
Transplantationauthors
Motomura N,Lou H,Orskov H,Ramwell PW,Foegh MLdoi
10.1097/00007890-199804270-00003subject
Has Abstractpub_date
1998-04-27 00:00:00pages
1024-30issue
8eissn
0041-1337issn
1534-6080journal_volume
65pub_type
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