VASCULAR IRON DEPOSITION & DIABETIC COMPLICATIONS

血管铁沉积

• 批准号: 6118861
• 负责人: JOHN W EATON
• 金额: $ 0.49万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118861
• 关键词: Mammalia; bioengineering /biomedical engineering; biological products; biomedical resource; lipids

Humans and animals with diabetes develop peripheral nerve and vascular dysfunction. Interestingly, the early nerve blood flow and nerve conduction deficits in diabetic animals are fully corrected by administration of iron chelators such as desferrioxamine and trientine. As a potential explanation for this rather surprising effect of iron chelators, we hypothesize the following sequence of events (i) Elevated sugars lead to enhanced protein glycation, particularly in long-lived proteins such as elastin and collagen which are major constituents of the internal elastic laminae. (ii) Glycation of elastin and collagen produces structures which bind iron leading, in vivo, to the formation of a ferruginous barrier immediately beneath the endothelium. (iii) This iron-rich sub-endothelial protein matrix will - through iron-mediated processes - catalytically destroy endothelium-derived relaxing factor nitric oxide. (iv) The resultant defect in endothelium-dependent vascular r ela xation leads to vasoconstriction, chronic peripheral ischemia, and, finally, dysfunction and death of peripheral nerves. The objective of our experimental work with ESR are: (i) Attempt to determine the nature of the glycated protein:iron adducts(s), (ii) examine the extent to which these adducts interact with nitric oxide and, if possible, (iii) determine the life-span of the nitric oxide:iron:glycated protein complexes.

患有糖尿病的人类和动物会发展外周神经， 血管功能障碍 有趣的是，早期的神经血流量和 糖尿病动物中的神经传导缺陷被完全纠正， 施用铁螯合剂如去铁胺， Trientine。 作为一个可能的解释，这相当令人惊讶， 铁螯合剂的作用，我们假设以下顺序 事件（i）升高的糖导致增强的蛋白质糖化， 特别是在长寿命的蛋白质如弹性蛋白和胶原蛋白中， 是内弹性层的主要组成部分。 （二） 弹性蛋白和胶原蛋白的糖基化产生结合铁的结构 在体内导致铁质屏障的形成 就在内皮细胞下面。 (iii)这种富含铁的 内皮下蛋白质基质将通过铁介导的过程 - 催化破坏内皮源性舒张因子一氧化氮 环氧 (iv)由此导致的内皮依赖性血管反应的缺陷， ELA导致血管收缩，慢性外周缺血， 最后是周围神经的功能障碍和死亡。 的 我们的ESR实验工作的目标是：（i）尝试 确定糖化蛋白质的性质：铁加合物，（ii） 检查这些加合物与一氧化氮相互作用的程度 如果可能的话，（iii）确定硝酸的寿命 氧化物：铁：糖化蛋白复合物。