TNP-470, an angiogenesis inhibitor, attenuates the development of allograft vasculopathy

Mark D. Denton, Colm Magee, Michael Melter, Vikas R. Dharnidharka, Mohamed H. Sayegh, David M. Briscoe

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Fischer 344 rat recipients of Lewis allografts were treated with TNP-470, a synthetic fumagillin derivative and a well-established angiogenesis inhibitor. TNP-470 alone resulted in some prolongation of graft survival as compared with untreated recipients, but all grafts ultimately failed. In contrast, treatment with cyclosporine (CsA) from day 0 to 30 resulted in prolonged graft survival and marked cardiac allograft vasculopathy (CAV) by histology (mean score 2.28±0.2). There were many neovessels within the intima of CAV lesions. When TNP-470 was administered in combination with CsA from day 0 to 30, the degree of CAV was similar to that with CsA alone (mean score 2.22±0.26). However, when TNP-470 was administered from day 30 to 120 after discontinuation of CsA, there was a marked reduction in the degree of CAV (mean score 1.08±0.11). Therefore, TNP-470 interrupts the progression of CAV when given late but does not prevent its development when given immediately posttransplantation.

Original languageEnglish
Pages (from-to)1218-1221
Number of pages4
JournalTransplantation
Volume78
Issue number8
DOIs
StatePublished - Oct 27 2004

Keywords

  • Angiogenesis
  • Chronic rejection
  • Endothelial cells
  • Transplantation

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