CARDIOVASCULAR DISEASE AND MICROVASCULAR DYSFUNCTION IN FAT-FED RHESUS MONKEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 心血管并发症占糖尿病(DM)相关死亡率和发病率的绝大部分。这些并发症大致可分为大血管和微血管。糖尿病的微血管并发症往往对糖尿病患者的生活质量和生存造成毁灭性的影响。现在公认的是，许多微血管并发症与高血糖和胰岛素抵抗的程度直接相关。然而，我们对这些疾病的发病机制和适当治疗的了解是初步的。 早期发现微血管异常将有助于识别糖尿病、胰岛素抵抗或肥胖患者，这些患者是发生主要终末器官并发症的高危人群，谁可以从治疗干预中受益。一种常规评估微血管血流储备的方法也可用于早期识别外周血管疾病患者，这些患者适合进行血管重建术或其他治疗，类似于目前用于检测冠状动脉疾病的方案。尽管临床需要很大，但目前还没有一种可靠的、非侵入性的方法来评估患者周围组织的微血管或毛细血管水平的血流灌注。这项建议的总体目标是描述与饮食诱导的非人灵长类动物肥胖/胰岛素抵抗相关的微血管并发症，这些异常反应可以通过对比增强超声(CEU)来评估。这些研究正在使用非侵入性技术的组合来表征长期食用高脂肪饮食的恒河猴心血管疾病的水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular complications account for the vast majority of the mortality and morbidity associated with diabetes (DM). These complications can be broadly categorized as macrovascular and microvascular. Microvascular complications of DM often have devastating effects on the quality of life and survival for patients with diabetes. It is now well recognized that many of microvascular complications are directly related to the degree of hyperglycemia and insulin resistance. However, our understanding of the pathogenesis and appropriate treatment of these disorders is rudimentary. Early detection of microvascular abnormalities will be useful for identifying patients with DM, insulin resistance, or obesity who are at high risk for developing major end-organ complications and who could benefit from therapeutic intervention. A method for routinely assessing microvascular flow reserve could also be useful for early identification of patients with peripheral vascular disease who are candidates for revascularization or other treatments, similar to protocols that are currently employed for the detection of coronary artery disease. Despite the great clinical need, a reliable, non-invasive method capable of assessing perfusion of peripheral tissues at the microvascular or capillary level in patients is currently not available. The overall aim of this proposal is to characterize the microvascular complications are associated with diet induced obesity/insulin resistance in the nonhuman primate (NHP) and that these abnormal responses can be assessed by contrast-enhanced ultrasound (CEU). These studies are using a combination of noninvasive techniques to characterize the level of cardiovascular disease in rhesus macaques chronically consuming a high fat diet.