Epidemiology: Oxidative Stress and Early Atherosclerosis

描述(申请人提供)：氧化应激与炎症和内皮功能障碍有关，与肥胖、血糖和吸烟等疾病相互作用。这种氧化应激，即使是在年轻的成年人，可能在临床疾病之前很久就导致了长期的疾病风险。为了解决这些问题，我们建议继续使用R01 HL053560，当地称为青年抗氧化剂纵向趋势(YALTA)。雅尔塔自1995年以来一直得到资助，作为青年冠状动脉风险发展(CARDIA)的辅助项目，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名年龄在18-30岁的黑人和白人男性和女性)在第20年的第7次考试中保留了72%的参与者，并于2010年开始第25年的后续行动。雅尔塔的主要目的是通过与CARDIA完整的数据库集成，无缝获取更多的样本和生物化学来确定氧化损伤及其后果。雅尔塔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)。雅尔塔在CARDIA 0年和20年期间检测了20多个与氧化有关的指标，因此可以确定这些变量在疾病风险中变得重要的时间框架。我们之前的测量提供了与氧化应激和疾病风险增加相关的指标概况。我们建议重复检测几个信息标志物，包括氧化型低密度脂蛋白、细胞间黏附分子-1(ICAM1)、F2-异前列腺素和HbA1C。此外，循环中的类胡萝卜素和脂联素也会反复出现。最近的技术进步允许引入新的指示剂，包括荧光氧化产物、几种氧化剂和抗氧化酶的RNA表达以及尿液代谢谱，这将提供有关饮食摄入量和类黄酮类代谢的信息。这些指标将提供新的信息，对于我们理解氧化应激的演变及其与肥胖、炎症、氧化剂来源和饮食摄入量之间的相互作用在疾病风险中至关重要。我们假设，氧化损伤和抗氧化剂状态差的指标将与营养丰富的饮食摄入量低、缺乏体育活动、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，无论是单独的还是联合的，都将与疾病风险相关。尿代谢谱将与营养丰富的食物的饮食摄入量和疾病风险相关。肥胖会影响一些与氧化有关的活动，这些关系将通过这项研究来确定。雅尔塔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，并有助于确定迫切需要改变其氧化状态的年轻人，以便他们能够长期受益于氧化应激的减少。 公共卫生相关性：动脉粥样硬化和心血管疾病是主要的公共卫生问题，在美国仍然是主要的死亡原因。一个主要的病因可能是氧化损伤。雅尔塔，年轻人抗氧化剂的纵向趋势研究将继续确定年轻人和中年人的氧化相关因素及其与亚临床和临床心血管疾病的关系。

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. PUBLIC HEALTH RELEVANCE: Atherosclerosis and cardiovascular disease are major public health concerns and remain major causes of death in the United States. A major etiologic factor may be oxidative damage. The YALTA, Young Adult Longitudinal Trends in Antioxidants, study will continue to identify oxidation-related factors in young and middle-aged adults and their association with subclinical and clinical cardiovascular disease.