Role of Epigenetic Mechanisms in the Vascular Complications of Diabetes
Diabetes and metabolic disorders are leading causes of micro- and macrovascular complications. Furthermore, efforts to treat these complications are hampered by metabolic memory, a phenomenon in which prior exposure to hyperglycemia predisposes diabetic patients to the continued development of vascular diseases despite subsequent glycemic control. Persistently increased levels of oxidant stress and inflammatory genes are key features of these pathologies. Biochemical and molecular studies showed that hyperglycemia induced activation of NF-κB, signaling and actions of advanced glycation end products and other inflammatory mediators play key roles in the expression of pathological genes. In addition, epigenetic mechanisms such as posttranslational modification of histones and DNA methylation also play central roles in gene regulation by affecting chromatin structure and function. Recent studies have suggested that dysregulation of such epigenetic mechanisms may be involved in metabolic memory leading to persistent changes in the expression of genes associated with diabetic vascular complications. Further exploration of these mechanisms by also taking advantages of recent advances in high throughput epigenomics technologies will greatly increase our understanding of epigenetic variations in diabetes and its complications. This in turn can lead to the development of novel new therapies.
KeywordsVascular Smooth Muscle Cell Histone Modification Vascular Complication Epigenetic Mechanism Inflammatory Gene
The authors gratefully acknowledge grant support from the National Institutes of Health (NIDDK and NHLBI), the Juvenile Diabetes Research Foundation, and the American Diabetes Association.
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