Organ Transplantation Research - Risks, Prognosis, Procedure, Surgery

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Vitamin E in heart transplantation: effects on cardiac gene expression.

Schulte I, Bektas H, Klempnauer J, Borlak J

Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology, Hannover, Germany.

BACKGROUND: Oxidative stress, as induced in organ storage or upon reperfusion, may impact the quality of the transplant. Vitamin E, a radical scavenger, may alleviate stress associated with cardiac surgery. METHODS: We investigated the effects of vitamin E treatment in a rat heart transplantation model and link dose to tissue and plasma vitamin E levels. We further studied expression of 39 genes coding for stress markers, proinflammatory cytokines, apoptotic pathways, structural proteins, extracellular matrix, cardiomyocyte specific transcription factors, and metabolic pathways to obtain information on the benefits of vitamin E treatment. RESULTS: Treatment of donor and recipient animals significantly increased blood and heart tissue vitamin E levels (P<0.05). We observed a significant reduction (P<0.05) of genes coding for oxygen detoxification (e.g., SOD), as well as expression of the adhesion molecules, ICAM-1 and PECAM-1 (P<0.05). Notably, transcript levels of the stress marker atrial natriuretic peptide (ANP) was reduced (P<0.05), whereas expression of cardiac and skeletal actin was increased. Further, expression of the disease markers beta-MHC and VCAM-1 was repressed (P<0.05), as was expression of the myocyte enhancer factor MEF2c. Noteworthy, vitamin E repressed expression of SP1 and c-fos transcript level. Specifically, their expression is elevated in reperfusion injured tissue. CONCLUSIONS: Based on transcript profiling, we propose a novel role of vitamin E in transplant surgery. Our findings warrant further studies to explore its clinical application.

Published 14 March 2006 in Transplantation, 81(5): 736-45.
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