Prof. Johannes Waltenberger,
Epigenetics relates to changes in gene expression that do not involve changes in gene sequences. In recent years, three mechanisms of epigenetic modifications have been identified: 1) DNA methylation, 2) Histone modifications, 3) Non-coding small RNAs. In addition, it is interesting to note that such changes can occur rather fast. During a very interesting symposium at the ESC congress in Stockholm, Dr. M.E. Symonds from Nottingham, GB, highlighted the relation between low birth-weight, e.g. secondary to maternal nutrient restriction, and obesity and insulin resistance of the offspring resulting in a higher cardiovascular mortality. This aspect was further elucidated by Dr. R. Gemke from Amsterdam, NL. Dr. S. Yla-Herttuala from Kuopio, FI, presented interesting insights into the role of epigenetics in the pathogenesis of atherosclerosis. He demonstrated that hypomethylation is present in atherosclerotic plaques at a magnitude otherwise seen in malignant tumors. This hypomethylation is relevant as it is associated with enhanced proliferation secondary to increased transcriptional activity. Likewise, the activity of the angiogenic factor VEGF is controlled and facilitated by small RNA species such as siRNA and shRNA. Besides atherosclerosis, other cardiovascular conditions including heart failure and thrombophilia are partly controlled by epigenetic mechanisms, as Dr. R. Foo from Cambridge, UK, pointed out in his presentation. It is important to note that these mechanisms may even be influenced by therapeutic interventions. One such example is the use of folic acid, which may influence methylation and thereby control or modifiy gene expression to treat cardiac and vascular diseases.
Epigenetics of cardiovascular disease
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