10.1. Introduction
Cardiovascular diseases (CVD) are polygenic in nature. Many genes involved in lipid metabolism, vascular homeostasis, hemostasis, oxidative stress, and inflammation have been found to be related to cardiovascular diseases. Vascular homeostasis is regulated by a delicate balance between proliferation, apoptosis, differentiation of vascular cells, and control of endothelial cell-mediated recruitment of inflammatory and immune cells. In the last decade, it has become clear that epigenetic processes play a central role in regulating the gene-environmental interactions. Epigenetics describes meiotically and mitotically heritable changes in gene expression patterns as a result of chromatin modifications without changes in the actual DNA sequence. Chromatin modifications include methylation of DNA at CpG dinucleotides and rearrangement of nucleosomes as a result of covalent posttranslational modifications of histone tails such as acetylation, methylation, ubiquitination and SUMOylation of lysine residues, phosphorylation of serine residues, and methylation of arginines. These modifications act by changing the accessibility of chromatin to transcription factors and by regulating the recruitment of coregulators to target genes. Pharmacologic studies as well as gain and loss of function studies have shown that epigenetic modifiers such as histone acetyltransferases (HATs) and deacetylases (HDACs), histone methyltransferases (HMTs), and demethylases (HDs) as well as DNA methyltransferases (DNMTs) may mediate the pathogenesis of many vascular diseases. Furthermore, many genes involved in the pathogenesis of CVD have been shown to be epigenetically regulated. This suggests a potential role of epigenetic therapy in the control of these diseases. This chapter is structured in four parts. After a general presentation of the epigenetic theory of cardiovascular risk factors, we will discuss the role of the epigenetic modifiers in the pathogenesis of CVD, the epigenetic regulation of cardiovascular genes, and the potential of using epigenetic therapy such as HDAC, HMT, HD, and DNMT inhibitors in the control of CVD.