Hyperhomocysteinemia, DNA methylation and vascular disease

Abstract

AbstractHyperhomocysteinemia (HHcy) has been established as a potent independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is largely unknown. We were the first to propose that hypomethylation is the key biochemical mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We reported that clinically relevant concentrations of Hcy (10–50 μmol/L) exerts highly selective inhibitory effects on cyclin A transcription and EC growth through a hypomethylation related mechanism, which blocks cell cycle progression and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading to cyclin A chromatin remodeling. We found that adenovirus-transducedClin Chem Lab Med 2007;45:1660–6.