Expression of heme oxygenase-1 can determine cardiac xenograft survival

M. P. Soares, Y. Lin, J. Anrather, E. Csizmadia, K. Takigami, K. Sato, S. T. Grey, R. B. Colvin, Augustine M K Choi , K. D. Poss, F. H. Bach

Research output: Contribution to journalArticle

542 Scopus citations

Abstract

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) (refs. 7-10). 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 heine 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.

Original languageEnglish (US)
Pages (from-to)1073-1077
Number of pages5
JournalNature Medicine
Volume4
Issue number9
DOIs
StatePublished - Sep 1 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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