TY - JOUR
T1 - Murine cytomegalovirus infection leads to increased levels of transplant arteriosclerosis in a murine aortic allograft model
AU - Heim, Christian
AU - Abele-Ohl, Silke
AU - Eckl, Sebastian
AU - Ramsperger-Gleixner, Martina
AU - Mahmoudian, Shohreh
AU - Weyand, Michael
AU - Stamminger, Thomas
AU - Ensminger, Stephan M.
PY - 2010/8/27
Y1 - 2010/8/27
N2 - Introduction. Cytomegalovirus infection after heart transplantation is considered as risk factor for the development of transplant arteriosclerosis. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus (MCMV) as a single risk factor on transplant arteriosclerosis in an experimental aortic allograft model. Methods. Major histocompatibility complex class I-mismatched aortas of C.B10-H2(b)/LilMcdJ donor were transplanted into BALB/c recipients, which were either mock-infected or infected with MCMV (strain Smith) on day 7 and harvested 37 days after transplantation. In one experimental group animals received a daily dose of everolimus to increase the viral load of recipients. Grafts were analyzed by histology, morphometry, and immunofluorescence. Intragraft cytokine mRNA production was analyzed by real-time polymerase chain reaction (PCR), and persistence of cytomegalovirus infection was confirmed by TaqMan PCR. Results. After infection with MCMV, there was significantly more intimal proliferation when compared with uninfected controls (intimal proliferation 83.5%±9.6% [MCMV+] vs. 43.9%±5.1% [MCMV+]), indicating that MCMV plays a role in the development of transplant arteriosclerosis. Even after treatment with everolimus, MCMV infection pronounced significantly more intimal proliferation (intimal proliferation 52.5%±7.3% [MCMV+] vs. 20.2%±1.7% [MCMV+]). Intragraft mRNA expression showed significantly higher production of CD62E, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 after infection with MCMV. Cellular infiltration revealed significantly more CD4+, CD8+, and dendritic cells. 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. Conclusion. These data suggest that MCMV infection plays an important role in the development of transplant arteriosclerosis.
AB - Introduction. Cytomegalovirus infection after heart transplantation is considered as risk factor for the development of transplant arteriosclerosis. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus (MCMV) as a single risk factor on transplant arteriosclerosis in an experimental aortic allograft model. Methods. Major histocompatibility complex class I-mismatched aortas of C.B10-H2(b)/LilMcdJ donor were transplanted into BALB/c recipients, which were either mock-infected or infected with MCMV (strain Smith) on day 7 and harvested 37 days after transplantation. In one experimental group animals received a daily dose of everolimus to increase the viral load of recipients. Grafts were analyzed by histology, morphometry, and immunofluorescence. Intragraft cytokine mRNA production was analyzed by real-time polymerase chain reaction (PCR), and persistence of cytomegalovirus infection was confirmed by TaqMan PCR. Results. After infection with MCMV, there was significantly more intimal proliferation when compared with uninfected controls (intimal proliferation 83.5%±9.6% [MCMV+] vs. 43.9%±5.1% [MCMV+]), indicating that MCMV plays a role in the development of transplant arteriosclerosis. Even after treatment with everolimus, MCMV infection pronounced significantly more intimal proliferation (intimal proliferation 52.5%±7.3% [MCMV+] vs. 20.2%±1.7% [MCMV+]). Intragraft mRNA expression showed significantly higher production of CD62E, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 after infection with MCMV. Cellular infiltration revealed significantly more CD4+, CD8+, and dendritic cells. 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. Conclusion. These data suggest that MCMV infection plays an important role in the development of transplant arteriosclerosis.
UR - http://www.scopus.com/inward/record.url?scp=77955984827&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e3181e8a699
DO - 10.1097/TP.0b013e3181e8a699
M3 - Journal articles
C2 - 20585280
AN - SCOPUS:77955984827
VL - 90
SP - 373
EP - 379
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 4
ER -