26S PROTEASOME AND ENDOTHELIAL DYSFUNCTION IN DIABETES

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 涉及心脏或血管的疾病（心血管疾病）有一个共同的特点  失去正常的血管功能。血管功能的丧失是心血管疾病的第一步，如中风或心脏病发作。然而，目前尚不清楚血管首先是如何生病的。为了了解血管在糖尿病中如何失去功能，我们将研究重点放在诺贝尔奖发现（2004年）上：一种切碎机（称为26 S蛋白酶体），它可以控制我们身体的蛋白质质量和数量。重要的是，新出现的数据表明，未能控制机器与糖尿病患者的血管疾病有关。我们的研究提供了第一个证据，在整个动物，糖尿病增强了这台机器的切碎能力，并开始了解这是如何发生的。我们将进一步研究如何防止这种情况发生。在完全了解血管功能障碍的机制后，我们将能够找到疾病预防的选择，并允许患者从疾病状况中恢复到最大程度。此外，它还有助于确定糖尿病及其并发症血管健康的新药。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diseases that involve heart or blood vessels (cardiovascular diseases) share a common trait  loss of normal blood vessel function. The loss of vessel function is the first step toward cardiovascular disorders, such as stroke or heart attack. Yet it is not clear how the blood vessels become sick in the first place. To understand how blood vessels lose their function in diabetes, we have focused our research on a Nobel Prize discovery (2004): a chopping machine (called the 26S proteasome) that keeps protein quality and quantity of our bodies in check. Importantly, emerging data suggest that failure to control the machine is associated with vessel illness in diabetes. Our studies provide the first evidence in whole animal that diabetes enhances the chopping capacity of this machine and start to understand how this happens. We will further find out how we can prevent this from happening. Upon complete understanding of the mechanisms underlying vessel dysfunction, we would be able to find options for disease prevention and allow patients to recover to the maximum from illness conditions. Furthermore, it also helps to identify new drugs for vascular health in diabetes and its complications.