Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease.
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.
Pons
Douwe
D
Department of Cardiology, Leiden University Medical Center, C5-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
de Vries
Florentine R
FR
van den Elsen
Peter J
PJ
Heijmans
Bastiaan T
BT
Quax
Paul H A
PH
Jukema
J Wouter
JW
D000107:Acetylation; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D005109:Extracellular Matrix / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000502:physiology*; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D051548:Histone Acetyltransferases; D006655:Histone Deacetylases