Methylation and Atherosclerosis

Epigenetic modification is an important biochemical mechanism used to maintain normal development and biological function without changing the primary DNA sequence. DNA and histone methylations are the key epigenetic regulation, essential for embryonic development and control of gene expression. Emerging evidence has demonstrated that aberrant methylation patterns of DNA and histones result in many diseases, including cardiovascular disease (CVD), cancer, Alzheimer's disease, diabetes, and autoimmune disease. Methylation is a reversible biochemical procedure catalyzed by methyltransferases which transfer a methyl group from s-adenosyl methionine (SAM) to DNA, RNA, protein or phospholipids. After donating the methyl group, SAM is converted to s-adenosyl homocysteine (SAH) and further metabolized to homocysteine (Hcy), which modulates cellular methylation. Increased plasma homocysteine is a potent risk factor for CVD, diabetes and Alzeimer's disease. In this chapter, we will introduce the molecular mechanisms in DNA and protein methylation regulation and highlight the role of aberrant DNA and protein methylation in atherosclerosis. We will also discuss the biochemical basis of Hcy metabolism and the regulation of methylation. Finally, we will describe hypomethylation as a biochemical mechanism mediating hyperhomocysteinemia-induced CVD.