Epidemiology: Oxidative Stress and Early Atherosclerosis

流行病学：氧化应激和早期动脉粥样硬化

• 批准号: 8474821
• 负责人: Myron D Gross
• 金额: $ 69.43万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8474821
• 关键词: Address; Adult; Age; Antioxidants; Atherosclerosis; Berry; Biochemical; Biochemistry; Biological Assay; Blood Pressure; Body mass index; Cardiovascular Diseases; Carotenoids; Carotid Arteries; Cause of Death; Cholesterol; Clinical; Coronary artery; DNA; Databases; Development; Diabetes Mellitus; Diet; Dietary Fiber; Dietary Flavonoid; Dietary Practices; Dietary intake; Disease; Dyslipidemias; Eating; Edible Plants; Enzyme Gene; Enzymes; Epidemiology; Etiology; Evaluation; Evolution; F2-Isoprostanes; Flavonoids; Food; Functional disorder; Funding; Gene Expression; Genes; Genetic Transcription; Hippuric acid; Hypertension; Individual; Inflammation; Intake; Intercellular Adhesion Molecules; Intercellular adhesion molecule 1; Joints; Kidney Diseases; Laboratories; Link; Lipids; Lipoxygenase; Lung diseases; Maintenance; Measurement; Measures; Metabolic; Metabolic syndrome; Metabolism; Nutrient; Nuts; Obesity; Oxidants; Oxidases; Oxidative Stress; Participant; Pathogenesis; Pattern; Population; Process; Proteins; Public Health; Publications; Reactive Oxygen Species; Research Infrastructure; Risk; Risk Factors; Role; Sampling; Serum; Smoking; Source; Specificity; Staging; Superoxide Dismutase; Testing; Thick; Time; Transferase; United States; Weight; Woman; adiponectin; aged; cardiovascular disorder risk; cohort; coronary artery calcification; cost; disorder risk; fruits and vegetables; glycation; good diet; insight; intima media; men; middle age; novel; nutrient metabolism; oxidation; oxidative damage; oxidized low density lipoprotein; public health relevance; trend; urinary; young adult

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.

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、血糖和吸烟等病症相互作用。这种氧化应激，即使在青年时期，也可能早在临床疾病发生之前就导致长期疾病风险。为了解决这些问题，我们建议延续 R01 HL053560，当地称为年轻人抗氧化剂纵向趋势 (YALTA)。雅尔塔自 1995 年以来一直得到持续资助，作为年轻人冠状动脉风险发展 (CARDIA) 的附属项目，从而利用其基础设施实现成本效率和最小化参与者负担。 CARDIA（1985-86 年，n=5115 名 18-30 岁的黑人和白人男性和女性）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 年的随访。雅尔塔的中心目的是确定氧化损伤及其影响通过无缝获取额外的样本和生物化学，与完整的 CARDIA 数据库集成来产生后果。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）。 YALTA 在 CARDIA 第 0 年和第 20 年期间检测了 20 多种与氧化相关的指标，因此可以确定这些变量在疾病风险中变得重要的时间范围。我们之前的测量提供了与氧化应激升高和疾病风险相关的指标概况。我们建议重复测量多种信息标记物，包括氧化 LDL、细胞间粘附分子 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 表达以及尿液代谢谱，这将提供有关饮食摄入和类黄酮代谢的信息。这些指标将提供新的信息，对于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中的饮食摄入的相互作用至关重要。我们假设氧化损伤和抗氧化状态不佳的指标与营养丰富的饮食摄入量低、缺乏身体活动、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。氧化应激的单独和组合测量将与疾病风险相关。尿液代谢特征与营养丰富的食物的饮食摄入量和疾病风险有关。一些与氧化相关的活动受到肥胖的影响，这些关系将通过研究确定。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，并确定迫切需要有利地改变氧化状态的年轻人，以便他们能够从氧化应激的减少中长期受益。