MECHANISMS OF VASCULAR DYSFUNCTION IN OBESITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在过去的十年里，儿童肥胖在美国急剧增加。 不幸的是，这些超重的儿童面临着靶器官损伤、成人糖尿病、心脏病和中风的风险。 脂联素（APN）是一种脂肪组织来源的细胞因子，是肥胖引起靶器官损伤的途径之一。 APN具有直接的血管保护作用。 然而，它在肥胖症、肥胖相关炎症和冠状动脉疾病中的水平降低。 低水平与胰岛素抵抗和血脂异常有关，血脂异常是代谢综合征的一部分。 因此，我们提出了一个横断面研究学龄青少年肥胖和血管功能之间的关系进行研究。 将进行分析，以确定动脉功能障碍的潜在机制是否与CV风险因子、炎症和APN水平异常相关。 将在普林斯顿学区正在进行的“进展为2型糖尿病的里程碑”研究（N=2000）中测量肱动脉扩张性、BMI、BP、血脂、高灵敏度CRP和APN。 该队列的样本（n=450）也将接受肱动脉血流介导的扩张，测量增强指数和脉搏波速度。 将在正常人、胰岛素水平正常的肥胖受试者和高胰岛素血症的肥胖青少年之间进行实验室和血管测量的对比。 表明与超重相关的代谢异常导致儿童血管功能障碍，将有助于医生识别高危儿童进行早期治疗，以防止未来的心脏病发作和中风。

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. Childhood obesity has increased dramatically in the U.S. in the last decade. Unfortunately, these overweight children are at risk for target organ damage, adult diabetes, heart disease and stroke. One of the pathways by which obesity may induce target organ damage involves adiponectin (APN) an adipose-tissue derived cytokine. APN has direct vascular protective effects. However, it is found in reduced levels in obesity, obesity related inflammation and in coronary artery disease. Low levels are associated with insulin resistance and the dyslipidemia found as part of the metabolic syndrome. Therefore, we propose a cross-sectional study of school aged adolescents to study relationships between obesity and vascular function. Analyses will be performed to determine if the mechanisms underlying arterial dysfunction may relate to abnormal levels of CV risk factors, inflammation and APN. Brachial Artery Distensibility, BMI, BP, lipids, high sensitivity CRP, and APN will be measured in the ongoing 'Landmarks in the Progression to Type 2 Diabetes' study currently being conducted in the Princeton School District (N=2000). A sample of this cohort (n=450) will also undergo brachial flow mediated dilatation, measurement of augmentation index & pulse wave velocity. Contrasts in laboratory and vascular measures will be made among normals, obese subjects with normal insulin levels and obese adolescents with hyperinsulinemia. Showing that metabolic abnormalities related to overweight lead to blood vessel dysfunction in children will help doctors identify high risk children for early treatment to prevent future heart attack and stroke.