Role of epigenetic mechanisms in diabetic vascular complications

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Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called oxidation pathways, interferes with enzymes which affect the structure of DNA and related molecules resulting in altered expression of many proteins. One of these proteins known as NF kappa B is activated in diabetes, probably by mechanisms involving regulation of these enzymes which play a central role in modifying gene structure. By clarifying the exact mechanisms at a molecular level that mediate the effect of glucose on genes and proteins it will be possible to target these molecules and develop new treatments to prevent, retard or reverse the blood vessel complications that are so common in diabetes.