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DOI: 10.1055/s-0029-1247066
Murine cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a murine aortic allograft model
Objectives: In clinical studies cytomegalovirus infection after heart transplantation is considered as risk factor for developing transplant arteriosclerosis, the hallmark feature of chronic rejection. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus on transplant arteriosclerosis in an experimental aortic allograft model in the absence of immune suppression.
Methods: MHC-class-I mismatched C.B10-H2(b)/LilMcdJ donor aortas were transplanted into BALB/c mice. Recipients were infected with an isolate of MCMV (Smith, ATCC VR-194) for 7 days and harvested 30 days after transplantation. Grafts were analyzed by histology and morphometry and persistence cytomegalovirus infection was confirmed by Taqman-PCR.
Results: Significant amounts of transplant arteriosclerosis were present in both experimental groups. After infection with MCMV there was significantly more intimal proliferation as compared to uninfected controls [intimal proliferation 72±11% (MCMV+) vs. 46±13% (MCMV-)] indicating that murine cytomegalovirus as an important risk factor for the development of transplant arteriosclerosis. In addition we could also confirm the presence of MCMV for the duration of the experimental protocol by PCR within the spleen, liver, salivary glands, lung and the aortic transplant itself. Immunohistological analysis revealed marked differences in leukocyte infiltration and adhesion molecule expression (ICAM-1) in the presence of MCMV infection.
Conclusion: These data suggest that murine cytomegalovirus infection plays an important role in the development of transplant arteriosclerosis.