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.
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