ROLE OF XANTHINE OXIDASE IN THE AGE-RELATED DECLINE IN FLOW-MEDIATED DILATION

黄嘌呤氧化酶在与年龄相关的血流介导的扩张下降中的作用

• 批准号: 7377884
• 负责人: DOUGLAS R SEALS
• 金额: $ 0.37万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377884
• 关键词: ROLE; XANTHINE; OXIDASE; AGE; RELATED

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. Flow-mediated dilation (FMD) reflects the ability of the vascular endothelium to produce vasodilation in response to physiological increases in shear stress or blood flow. It is primarily mediated by the release of vascular endothelial derived nitric oxide (NO). Brachial FMD is reduced in many types of cardiovascular diseases (CVD). Brachial FMD correlates with coronary vascular endothelial function and predicts future cardiovascular events in patients with CVD. FMD also decreases with age, which may contribute to the increased prevalence of CVD in older adults. Therefore, identifying the mechanisms involved in the impairment of brachial FMD with age has important clinical implications. Experimental evidence sugessts that xanthine oxidase (XO) induced oxidative stress plays a critical role in impaired FMD in patients with cardiovascular diseases. Because advancing age is also associated with increased oxidative stress level, it is possible that at least part of the increased oxidative stress within the arterial wall seen with age may be due to an increased formation of ROS by XO, contributing to the age-related decline in FMD. Consequently, the specific aim of this study is to measure FMD before and after XO oxidase blockade with allopurinol in young and older sedentary adults.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。血流介导的扩张（FMD）反映了血管内皮响应剪切应力或血流的生理增加而产生血管舒张的能力。它主要由血管内皮源性一氧化氮（NO）的释放介导。许多类型的心血管疾病 (CVD) 中的肱动脉 FMD 都会减少。肱动脉 FMD 与冠状血管内皮功能相关，可预测 CVD 患者未来的心血管事件。 FMD 也会随着年龄的增长而减少，这可能导致老年人 CVD 患病率增加。因此，确定随着年龄增长导致肱骨 FMD 损伤的机制具有重要的临床意义。 实验证据表明，黄嘌呤氧化酶 (XO) 诱导的氧化应激在心血管疾病患者的 FMD 受损中发挥着关键作用。由于年龄增长也与氧化应激水平增加有关，因此随着年龄的增长，动脉壁内氧化应激增加的至少一部分可能是由于 XO 形成的 ROS 增加，从而导致与年龄相关的 FMD 下降。因此，本研究的具体目的是测量年轻人和老年人久坐不动的 XO 氧化酶阻断前后的 FMD。