Atherosclerosis, lipids, inflammation and epigenetics.

Current evidence strongly suggests that chronic inflammation is a landmark of atherosclerosis and that markers of inflammation are important predictors of cardiovascular events. A crucial question is how proinflammatory gene expression patterns are established and maintained in atherosclerosis. Epigenetic gene regulation is a relatively new kid on the block in the field of cardiovascular disease. Epigenetics provides attractive candidate disease mechanisms, as it in principle explains how diet, environment and lifestyle can impose aberrant gene expression patterns in an individual’s life time and even transgenerationally [1 ,2 ]. The importance of epigenetics in cardiovascular diseases has been suggested by the association of aberrant DNA methylation, one of the epigenetic modifications of the genome, with predisposition to, and natural history of, atherosclerosis [3 ]. These correlative studies need to be complemented by strong population-based and experimental evidence demonstrating a causative role of DNA methylation in atherogenesis. The study by Stenvinkel et al. [3 ] takes us one step in this direction. Stenvinkel et al. demonstrate that inflammation markers are associated with peripheral blood cell DNA hypermethylation in chronic kidney disease. Furthermore, DNA hypermethylation was associated with all-cause and cardiovascular mortality in patients at advanced chronic kidney disease stages. Strikingly, the study showed a correlation between the presence of cardiovascular disease or age and cardiovascular mortality by a univariate analysis, but both correlations were lost when adjusting for the contribution of DNA hypermethylation. Based on this, the authors bring forward the fascinating suggestion that DNA hypermethylation is a potential marker or even determinant of cardiovascular disease at least in that population. The results of the study are in agreement with previous observations by our group suggesting that DNA hypermethylation is a lipoproteininduced early event in atherogenesis [3 ].