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

Transplantation. 2004 Oct 27;78(8):1218-21. doi: 10.1097/01.tp.0000137266.30134.02.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abdomen
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Coronary Disease / etiology
  • Coronary Disease / pathology
  • Coronary Disease / prevention & control
  • Cyclohexanes
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Graft Survival / drug effects
  • Heart Transplantation* / adverse effects
  • Male
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / therapeutic use*
  • Transplantation, Heterotopic

Substances

  • Angiogenesis Inhibitors
  • Cyclohexanes
  • Sesquiterpenes
  • Cyclosporine
  • O-(Chloroacetylcarbamoyl)fumagillol