Expression of heme oxygenase-1 can determine cardiac xenograft survival Academic Article uri icon


MeSH Major

  • Graft Survival
  • Heart Transplantation
  • Heme Oxygenase (Decyclizing)
  • Transplantation, Heterologous


  • The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts. In concordant models, this type of rejection is prevented by brief complement inhibition by cobra venom factor (CVF) and sustained T-cell immunosuppression by cyclosporin A (CyA). Mouse hearts that survive indefinitely in rats treated with CVF plus CyA express the anti-inflammatory gene heme oxygenase-1 (HO-1) in their endothelial cells and smooth muscle cells. The anti-inflammatory properties of HO-1 are thought to rely on the ability of this enzyme to degrade heme and generate bilirubin, free iron and carbon monoxide. Bilirubin is a potent anti-oxidant, free iron upregulates the transcription of the cytoprotective gene, ferritin, and carbon monoxide is thought to be essential in regulating vascular relaxation in a manner similar to nitric oxide. We show here that the expression of the HO-1 gene is functionally associated with xenograft survival, and that rapid expression of HO-1 in cardiac xenografts can be essential to ensure long-term xenograft survival.

publication date

  • September 1998



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1038/2063

PubMed ID

  • 9734404

Additional Document Info

start page

  • 1073

end page

  • 7


  • 4


  • 9