Epidemiology: Oxidative Stress and Early Atherosclerosis

描述（由申请人提供）：氧化应激与炎症和内皮功能障碍有关，与肥胖、吸烟和吸烟等疾病相互作用。这种氧化应激，即使在年轻的成年期，可能有助于长期的疾病风险早在临床疾病。为了解决这些问题，我们建议继续R 01 HL 053560，当地称为年轻成人抗氧化剂纵向趋势（YALTA）。自1995年以来，YALTA一直得到资助，辅助年轻人冠状动脉风险发展（CARDIA），从而利用其基础设施实现成本效益和最小的参与者负担。CARDIA（1985-86年，5115名18-30岁的黑人和白色男性和女性）在第20年的第7次检查中保留了72%的参与者，并于2010年开始第25年随访。YALTA的核心目的是通过无缝获取额外的样本和生化分析，与完整的CARDIA数据库集成，确定氧化损伤及其后果。YALTA研究氧化和疾病风险（代谢综合征、高血压、血脂异常、糖尿病、肾脏和肺部疾病、冠状动脉钙化、颈动脉壁厚度和超声心动图测量）。YALTA在CARDIA 0年和20年期间测定了20多种氧化相关指标，因此可以确定这些变量在疾病风险中变得重要的时间范围。我们先前的测量提供了与氧化应激和疾病风险升高相关的指标概况。我们建议重复测量几个信息标记物，包括氧化LDL，细胞间粘附分子-1（ICAM 1），F2-异前列腺素和HbA 1C。此外，循环类胡萝卜素和脂联素将被重复。最近的技术进步允许引入新的指标，包括荧光氧化产物，几种氧化剂和抗氧化酶的RNA表达和尿代谢谱，这将提供有关饮食摄入量和类黄酮代谢的信息。这些指标将为我们了解氧化应激的演变及其与肥胖、炎症、氧化剂来源和疾病风险饮食摄入的相互作用提供新的信息。我们假设氧化损伤和抗氧化状态差的指标与营养丰富的饮食摄入量低、缺乏运动、吸烟和肥胖有关。氧化剂和抗氧化酶基因表达的测量将与氧化应激及其后果相关。氧化应激的测量，单独和组合，将与疾病的风险。尿代谢谱将与营养丰富的食物的饮食摄入量和疾病的风险有关。一些与氧化有关的活动受到肥胖的影响，这些关系将由研究确定。YALTA最终将能够将氧化相关因素与临床疾病联系起来。这些研究将有助于确定可以改变氧化状态的因素，并确定迫切需要有利地改变其氧化状态的年轻人，以便他们可以从氧化应激的减少中长期受益。

DESCRIPTION (provided by applicant): Oxidative stress relates to inflammation and endothelial dysfunction, interacting with conditions such as adiposity, glycemia and smoking. Such oxidative stress, even in young adulthood, may contribute to long term disease risk long before clinical disease. To address these issues, we propose continuation of R01 HL053560, locally called Young Adult Longitudinal Trends in Antioxidants (YALTA). YALTA has been continuously funded since 1995, ancillary to Coronary Artery Risk Development in Young Adults (CARDIA), thus utilizing its infrastructure for cost efficiency and minimal participant burden. CARDIA (n=5115 black and white men and women aged 18-30 in 1985-86) retained 72% of participants at its 7th examination at year 20 and begins year 25 followup in 2010. YALTA's central purpose is to determine oxidative damage and its consequences by seamlessly obtaining additional samples and biochemistries, integrating with the full CARDIA database. YALTA studies oxidation and disease risk (metabolic syndrome, hypertension, dyslipidemia, diabetes, kidney and lung disease, coronary artery calcification, carotid artery wall thickness, and echocardiographic measures). YALTA has assayed over 20 oxidation-related indicators during CARDIA years 0 and 20 and can therefore define the timeframe when these variables become important in disease risk. Our previous measurements have provided a profile of indicators that are associated with elevated oxidative stress and disease risk. We propose to repeat measurement of several informative markers including oxidized LDL, intercellular adhesion molecule-1 (ICAM1), F2-isoprostanes, and HbA1C. In addition, circulating carotenoids and adiponectin will be repeated. Recent technological advances allow introduction of novel indicators, including fluorescent oxidation products, the RNA expression of several oxidant and antioxidant enzymes and a urinary metabolic profile, which will provide information on dietary intakes and flavonoid metabolism. These indicators will provide new information that is critical for our understanding of the evolution of oxidative stress and its interaction with obesity, inflammation, sources of oxidants and dietary intakes in disease risk. We hypothesize that indicators of oxidative damage and poor antioxidant status will be related to low intakes of nutrient-rich diets, physical inactivity, smoking and adiposity. Measurements of oxidant and antioxidant enzyme gene expression will be associated with oxidative stress and its consequences. The measurements of oxidative stress, singly and in combination, will be related to disease risk. The urinary metabolic profile will be related to dietary intakes of nutrient-rich foods and the risk of disease. Several oxidation-related activities are influenced by obesity and these relationships will be identified by the study. YALTA will ultimately be able to relate oxidation-related factors to clinical disease. These studies will aid in the identification of factors which can alter oxidation status and the identification of young adults with a critical need to favorably alter their oxidation status so that they can benefit in the long term from a reduction in oxidative stress.