Epigenetic modifications in cardiovascular disease.

Epigenetics represents a phenomenon of altered heritable phenotypic expression of genetic information occurring without changes in DNA sequence. Epigenetic modifications control embryonic development, differentiation and stem cell (re)programming. These modifications can be affected by exogenous stimuli (e.g., diabetic milieu, smoking) and oftentimes culminate in disease initiation. DNA methylation has been studied extensively and represents a well-understood epigenetic mechanism. During this process cytosine residues preceding a guanosine in the DNA sequence are methylated. CpG-islands are short-interspersed DNA sequences with clusters of CG sequences. The abnormal methylation of CpG islands in the promoter region of genes leads to a silencing of genetic information and finally to alteration of biological function. Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease. We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting.