Expression of heme oxygenase-1 can determine cardiac xenograft survival

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^1,2,3,4,5,6. 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. 7,8,9,10 ). 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^{9,11,12,13,14}. 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 monoxide¹⁵. Bilirubin is a potent anti-oxidant¹³, free iron upregulates the transcription of the cytoprotective gene, ferritin^{<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 16" title="Eisenstein, R.S., Garcia, M.D., Pettingell, W. & Munro, H.N. Regulation of...}