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* Medical Policlinic, Department of Medicine, University Hospital, Zürich, Switzerland;
Department of Clinical Research, University of Bern, Switzerland; and
Department of Anaesthesiology, University Hospital, Aachen, Germany
To whom requests for reprints should be addressed at 2 Medical Policlinic, Department of Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail: barton{at}usz.ch
Abstract
Endothelin regulates cytokine expression in vitro and in vivo. This study investigated the effects of chronic allograft rejection on hepatic endothelin-converting enzyme-1 (ECE-1) gene expression and endothelin-1 (ET-1) plasma clearance. Using the Lewis-F344 minor histocompatibility mismatch model of heterotopic cardiac transplantation, hepatic ECE-1 gene expression was measured by real-time polymerase chain reaction and host plasma clearance of ET-1 was measured 8 weeks after transplantation in the absence of immunosuppression. In animals undergoing allograft rejection, hepatic ECE-1 gene expression increased 2-fold (P < 0.05), whereas no effect of rejection on ET-1 clearance from plasma was observed. In summary, upregulation of ECE-1 gene expression occurs in the liver of the host during chronic allograft rejection. Because the liver represents both a key organ for cytokine production and for endothelin metabolism, increased hepatic ECE-1mediated ET-1 synthesis may contribute to host responses and cytokine production during allograft rejection.
Key Words: transplantation heart systemic organ ECE
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