Epigenetic Contribution to the Development and Progression of Vascular Diabetic Complications.

SIGNIFICANCE: The number of people suffering from diabetes worldwide is steadily rising. Complications from diabetes, including cardiovascular and renal disease, contribute to the high morbidity and mortality associated with this disease. Recent Advances: Hyperglycemia promotes tissue damage through diverse mechanisms involving increased production of reactive oxygen species. Increased oxidative stress drives changes in chromatin structure that mediate gene expression changes leading to the upregulation of proinflammatory and profibrotic mediators. The epigenetic contribution to diabetes-induced changes in gene expression is increasingly recognized as a key factor in the development and progression of vascular diabetic complications.

CRITICAL ISSUES: The mechanisms through which stimuli from the diabetic milieu promote epigenetic changes remain poorly understood. In addition, glycemic control constitutes an important factor influencing epigenetic states in diabetes, and the phenomenon of hyperglycemic memory warrants further research.

FUTURE DIRECTIONS: Knowledge of the molecular mechanisms underlying epigenetic changes in diabetes may allow the design of novel therapeutic strategies to reduce the burden of diabetic complications. Furthermore, certain epigenetic markers are detected early during the onset of diabetes and its complications and may prove useful as biomarkers for disease risk prediction.