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29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Evidence for epigenetic modification of sympathetic neuronal noradrenaline reuptake in essential

Epigenetische Modifikation der neuronalen Noradrenalin Wiederaufnahme bei essentieller Hypertonie

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  • M.P. Schlaich - Universitätsklinikum Erlangen (Erlangen, D)
  • E. Lambert - Baker Heart Research Institute Melbourne (Melbourne, AU)
  • M. Esler - Baker Heart Research Institute Melbourne (Melbourne, AU)
  • A. El-Osta - Baker Heart Research Institute Melbourne (Melbourne, AU)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP112

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch112.shtml

Published: August 8, 2006

© 2006 Schlaich et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Background: Noradrenaline transporter (NET) dysfunction has been proposed to contribute to increased noradrenaline spillover rates commonly present in essential hypertension, probably by amplifying the sympathetic neural signal. Despite extensive testing, no loss of function mutation has yet been identified in the human NET gene and the cause of the phenotype of impaired NET activity remains unknown.

Methods and Results: To further address this issue we assessed whether epigenetic mechanisms may account for impaired NET activity in 24 hypertensive patients with biochemical evidence of faulty neuronal noradrenaline reuptake, as opposed to 23 normotensive control subjects. After purification of genomic DNA and bisulfite modification, methylation of DNA was assessed by methylation specific real time PCR in selected CpG islands in the human NET promoter. Quantitative analysis revealed higher methylation levels in hypertensive patients with biochemical evidence of impaired neuronal noradrenaline reuptake when compared to normotensive control subjects (62 +/- 4 % vs 47 +/- 5%, p<0.001). Neuronal noradrenaline reuptake correlated inversely with % DNA methylation (r = -0.47, p < 0.05).

Conclusions: Our data indicate that epigenetic mechanisms contribute to alterations in neuronal noradrenaline reuptake and suggest that methylation-mediated gene silencing may account for impaired NET function in essential hypertension.