Expression of heme oxygenase-1 can determine cardiac xenograft survival

Nat Med. 1998 Sep;4(9):1073-7. doi: 10.1038/2063.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Complement Inactivator Proteins / pharmacology
  • Cyclosporine / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Elapid Venoms / pharmacology
  • Graft Rejection / immunology
  • Graft Survival / immunology*
  • Heart Transplantation / immunology*
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / physiology*
  • Heme Oxygenase-1
  • Immunosuppressive Agents / pharmacology
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myocardium / cytology
  • Rats
  • Transplantation, Heterologous / immunology*


  • Complement Inactivator Proteins
  • DNA-Binding Proteins
  • Elapid Venoms
  • Immunosuppressive Agents
  • Membrane Proteins
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • cobra venom factor
  • Cyclosporine
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse