Acceleration of arteriosclerosis of the rat aorta allograft by insulin growth factor-I.

We demonstrate here, for the first time, the mitogenic effect of insulin-like growth factor-I (IGF-I) on the development of transplant arteriosclerosis in a rat orthotopic aorta allotransplantation model (Brown Norway to Lewis). 125I-IGF-I uptake by the abdominal aorta of male Brown Norway rats occurred within 30 min. Consequently, we exposed the donor abdominal aorta to 0, 200, or 500 ng/ml IGF-I at 37 degrees C for 30 min ex vivo (n=7 per group), before transplantation. Fourteen days after transplantation, intimal thickening of the allografts in each of the three groups was 0.18+/-0.02 (IGF-I at 0 ng/ml), 0.23+/-0.03 (IGF-I at 200 ng/ml), and 0.30+/-0.03 (IGF-I at 500 ng/ml), respectively (mean+/-SEM, P<0.005 for 500 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation (cpm/microg protein) in the transplanted grafts at 7 days after transplantation (n=4 per group) was 40.6+/-7.6, 78.5+/-12.3, and 66.9+/-10.1, respectively (P<0.01 for 200 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation in the native thoracic aorta of the recipient was 23.4+/-4.4. We conclude that acceleration of allograft myointimal proliferation and intimal thickening was induced directly by IGF-I.