Activation of Adventitial Fibroblasts in the Early Stage of the Aortic Transplant Vasculopathy in Rat

Background. Transplant vasculopathy (TV) is the most significant obstacle to long-term success of organ transplantation. Increasing attention has been paid to the role of adventitia in vascular diseases. We evaluated the role of adventitial fibroblasts in the development of TV. Methods. Thoracic aortas from Sprague-Dawley (SD) rats transplanted into the abdominal aortas of Wistar rats worked as allografts, and isografts (SD to SD) were control. Grafts were removed on days 3, 7, and 14 for histologic, morphometric, and immunohistochemical detection of vimentin, alpha-smooth muscle actin, Ki-67, CD3, transforming growth factor-beta 1 (TGF-beta 1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-7 (MMP-7), and quantitative real-time reverse transcriptase polymerase chain reaction for TGF-beta 1, MCP-1, MMP-7, tumor necrosis factor-alpha, and interleukin-1 beta. Results. In the allografts, neointima thickness and neointima/media thickness ratios were slightly increased at 7 days and significantly increased at 14 days. Immunostaining of vimentin and alpha-smooth muscle actin showed adventitial fibroblasts activation and differentiation into myofibroblasts. Ki-67-positive nuclei were observed in the adventitia 3 days after allografting and subsequently in the neointima. No more than 4% CD3-positive cells were found in adventitia in all the groups. Compared with isografts, TGF-beta 1, MMP-7, and MCP-1 were expressed in the adventitia before neointima formation and were significantly increased in allografts at all time points. Tumor necrosis factor-alpha and interleukin-1 beta were also significantly increased in adventitia in allografts. Conclusions. These results demonstrated that adventitial fibroblasts are activated and can produce cytokines and chemokines before the neointimal hyperplasia. They may exert a potential effect on the development of neointimal hyperplasia in TV.