The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants

D. N. Streblow, C. N. Kreklywich, T. Andoh, A. V. Moses, J. Dumortier, P. P. Smith, V. Defilippis, K. Fruh, J. A. Nelson, S. L. Orloff

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalAmerican Journal of Transplantation
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2008

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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