Role of epigenetic mechanisms in the development of chronic complications of diabetes.

There is growing evidence that epigenetic regulation of gene expression including post-translational histone modifications (PTHMs), DNA methylation and microRNA (miRNA)-regulation of mRNA translation could play a crucial role in the development of chronic, diabetic complications. Hyperglycemia can induce an abnormal action of PTHMs and DNA methyltransferases as well as alter the levels of numerous miRNAs in endothelial cells, vascular smooth muscle cells, cardiomyocytes, retina, and renal cells. These epigenetic abnormalities result in changes in the expression of numerous genes contributing to effects such as development of chronic inflammation, impaired clearance of reactive oxygen species (ROS), endothelial cell dysfunction and/or the accumulation of extracellular matrix in the kidney, which causing the development of retinopathy, nephropathy or cardiomyopathy. Some epigenetic modifications, for example PTHMs and DNA methylation, become irreversible over time. Therefore, these processes have gained much attention in explaining the long-lasting detrimental consequences of hyperglycaemia causing the development of chronic complications even after improved glycaemic control is achieved. Our review suggests that the treatment of chronic complications should focus on erasing metabolic memory by targeting chromatin modification enzymes and by restoring miRNA levels.