Expression of heme oxygenase-1 can determine cardiac xenograft survival.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Soares, MP; Lin, Y; Anrather, J; Csizmadia, E; Takigami, K; Sato, K; Grey, ST; Colvin, RB; Choi, AM; Poss, KD; Bach, FH

Published Date

  • September 1998

Published In

Volume / Issue

  • 4 / 9

Start / End Page

  • 1073 - 1077

PubMed ID

  • 9734404

Pubmed Central ID

  • 9734404

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/2063

Language

  • eng

Conference Location

  • United States