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

• Published in: Transplantation Vol. 65; no. 8; p. 1024
• Main Authors: Motomura, N, Lou, H, Orskov, H, Ramwell, P W, Foegh, M L
• Format: Journal Article
• Language: English
• Published: United States 27.04.1998
• Subjects: Actins - analysis; Actins - biosynthesis; Animals; Aorta, Abdominal - metabolism; Aorta, Abdominal - pathology; Aorta, Abdominal - transplantation; Arteriosclerosis - pathology; Becaplermin; Fibroblast Growth Factor 2 - biosynthesis; Insulin-Like Growth Factor Binding Protein 1 - blood; Insulin-Like Growth Factor Binding Protein 2 - blood; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor Binding Protein 4 - blood; Insulin-Like Growth Factor Binding Proteins - biosynthesis; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Male; Platelet-Derived Growth Factor - biosynthesis; Proto-Oncogene Proteins c-sis; Rats; Rats, Inbred BN; Rats, Inbred Lew; Receptor, IGF Type 1 - biosynthesis; Time Factors; Transplantation, Homologous; Tunica Intima - metabolism; Tunica Intima - pathology; Tunica Intima - transplantation
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/00007890-199804270-00003

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. 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). 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. 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.