Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 8, Issue 2, Pages 277-287Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1600-6143.2007.02062.x
Keywords
accelerated rejection; allograft vasculopathy; angiogenesis; arrays; cardiac allograft rejection; cardiac allograft vasculopathy; chronic allograft rejection; cyclosporine A; cytomegalovirus (CMV); cytomegalovirus infection; transplant vascular sclerosis; virus
Categories
Funding
- NCRR NIH HHS [P51 RR000163-496162, P51 RR000163, P51 RR000163-486828] Funding Source: Medline
- NHLBI NIH HHS [R01 HL085451, HL083194, HL66238-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI070890, R01 AI070890-01A2] Funding Source: Medline
Ask authors/readers for more resources
Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real-time-polymerase chain reaction (RT-PCR) in an RCMV-accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV-infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21-28 days). Using a standard in vitro AG assay, virus and serum-free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock-infected cells. Supernatants from ultraviolet (UV)-inactivated RCMV-infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV-accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available