Role of epigenetic mechanisms in diabetic vascular complications

包括心脏病发作、中风、肾病和失明在内的糖尿病并发症似乎与高葡萄糖（糖）水平有关，但葡萄糖本身如何诱导终末器官损伤仍有待完全确定。在这一提议中，有人认为葡萄糖的长期破坏性影响与它通过直接影响DNA及其被称为组蛋白的覆盖物来破坏基因调节的能力有关。特别是葡萄糖，可能是通过改变某些被称为氧化途径的生化途径，干扰影响DNA和相关分子结构的酶，从而改变许多蛋白质的表达。其中一种被称为NF κ B的蛋白质在糖尿病中被激活，可能是由这些酶的调节机制引起的，这些酶在修饰基因结构中起着核心作用。通过在分子水平上阐明调节葡萄糖对基因和蛋白质影响的确切机制，将有可能针对这些分子并开发新的治疗方法，以预防、延缓或逆转糖尿病中常见的血管并发症。

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.