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European Heart Journal Advance Access originally published online on January 15, 2009
European Heart Journal 2009 30(3):266-277; doi:10.1093/eurheartj/ehn603
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease

Douwe Pons1,2, Florentine R. de Vries1, Peter J. van den Elsen3, Bastiaan T. Heijmans4, Paul H.A. Quax5 and J. Wouter Jukema1,2,6,*

1 Department of Cardiology, Leiden University Medical Center, C5-P, PO Box 9600, 2300 RC Leiden, The Netherlands
2 Interuniversity Cardiology, Institute of the Netherlands (ICIN), Utrecht, The Netherlands
3 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
4 Molecular Epidemiology Section, Leiden University Medical Center, Leiden, The Netherlands
5 TNO BioSciences, Gaubius Laboratory, Leiden, The Netherlands
6 Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands

Received 26 June 2008; revised 2 December 2008; accepted 17 December 2008; online publish-ahead-of-print 15 January 2009.

* Corresponding author. Tel: +31 71 526 20 20, Fax: +31 71 526 68 85, Email: j.w.jukema{at}lumc.nl

Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributing factors is the clinical and biological heterogeneity of these still life-threatening diseases, which involve processes that we do not fully understand at the moment. Over the past decades, it has become increasingly clear that part of the gene–environmental interactions relevant for complex diseases is regulated by epigenetic mechanisms such as histone acetylation and DNA methylation. Epigenetic processes modulate gene expression patterns without modifying the actual DNA sequence and have profound effects on the cellular repertoire of expressed genes. They contribute to the expression of genes that play a key role in extracellular matrix formation, inflammation, and proliferation, processes involved in cardiovascular pathologies such as atherosclerosis and restenosis.

Therefore, in this review, we argue that epigenetic regulators involved in histone acetylating and deacetylating activities contribute to the pathogenesis of atherosclerosis and restenosis. Furthermore, as alterations in chromatin structure are reversible, these epigenetic modifications are amendable to pharmacological intervention, which may prove to be an effective treatment modality for the management of cardiovascular diseases.

Key Words: Atherosclerosis • Restenosis • Epigenetics • Histone acetylation


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