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Increased Production of Cytokines and Growth Factors by Aortic Allografts: A Possible Explanation for Myointimal Hyperplasia Formation

Accelerated myointimal hyperplasia is a major complication of arterial allografts. The aim of our study was to analyze the role of growth factors in the genesis of myointimal hyperplasia in arterial allografts. Two groups of experiments were performed: Isografts and Allografts. The Isograft group consisted of 18 inbred Lewis rats in which a 1-cm long segment of aorta was inserted as abdominal aortic interposition graft. The aortic segments were obtained from syngeneic Lewis rats. The Allograft group consisted of 18 inbred Lewis rats, in which a 1-cm long segment of aorta was interposed at the level of the abdominal aorta. The aortic segments were obtained from allogeneic Brown-Norway rats. No immunosuppression was used. The animals were sacrificed 4 weeks after surgery and the aortic grafts were analyzed by light, electron microscopy (n = 3 for each group) and immunohistochemistry (n = 3 for each group). In addition, aortic segments (n = 12 for each group) were put in an organ culture to assess production of growth factors. All allografts showed evidence of severe myointimal hyperplasia, which was minimal in isografts. PDGF, bFGF and TGF-β1 production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts, whereas IL-1, TNF-α and GM-CSF production was increased in allografts and probably lymphocytes were the source of these cytokines (p < 0.001). We conclude that myointimal hyperplasia in aortic allografts is associated with an increase of IL-1, TNF-α and GM-CSF produced by lymphocytes.