Inflammatory suppression of endothelial function with aging and habitual exercise

衰老和习惯性运动对内皮功能的炎症抑制

• 批准号: 7663798
• 负责人: Ashley Elizabeth Walker
• 金额: $ 2.94万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7663798
• 关键词: Acute; Acute-Phase Proteins; Adult; Aerobic Exercise; Age; Aging; Anti-Inflammatory Agents; Antioxidants; Arteries; Ascorbic Acid; Aspirin; Blood Vessels; Cardiovascular Diseases; Cessation of life; Chronic; Clinical; Disease; Dose; Elderly; Endothelium; Enzymes; Exercise; Genes; Goals; Human; Impairment; Inflammation; Inflammatory; Infusion procedures; Intervention; Intravenous; Intravenous infusion procedures; Measurement; Measures; Mediating; Molecular; NF-kappa B; National Institute on Aging; National Research Service Awards; Oxidants; Oxidative Stress; Peripheral; Peripheral Blood Mononuclear Cell; Placebo Control; Placebos; Plasma; Production; Proteins; Reactive Oxygen Species; Research; Research Personnel; Research Project Grants; Research Support; Risk Factors; Signal Transduction; Translational Research; Vascular Endothelial Cell; Walkers; Woman; brachial artery; cardiovascular disorder prevention; career; career development; cytokine; human subject; improved; inflammatory marker; insight; men; peer; pre-doctoral; prevent; protein expression; public health relevance; salicylsalicylic acid; sedentary; transcription factor; young adult

DESCRIPTION (provided by applicant): This predoctoral NRSA proposal seeks support for research career development in the emerging, biomedically important field of "vascular aging". The career goal of the candidate, Ms. Walker, is to become an independent investigator in translational research focusing on the mechanisms mediating vascular aging in humans and interventions that prevent or reverse vascular aging. The proposed research project has important clinical implications for the prevention of cardiovascular disease (CVD) because vascular aging is now accepted as a major risk factor CVD. This project will focus on the reduction in vascular endothelial function, a key expression of vascular aging, as determined by measurement of endothelium-dependent dilation (EDO). EDD is markedly reduced with aging, even in healthy older adults, but the underlying mechanisms are incompletely understood. Chronic low-grade inflammation (with associated oxidative stress) is one possible mechanism that has not been directly investigated. In contrast to their sedentary peers, older adults who regularly perform aerobic exercise demonstrate largely preserved EDD. It is unknown if an absence of inflammation and associated oxidative stress-mediated suppression of EDD contributes to the preserved function in habitually exercising older adults. The influence of inflammation and oxidative stress on aging and age-associated diseases is a major research goal of the National Institute on Aging. To investigate these topics, groups of young and older healthy sedentary and habitually exercising men and women will be studied. The influence of inflammation on EDD (brachial artery flow-mediated dilation) will be determined by short-term inhibition of nuclear factor kappa B signaling with orally administered Salsalate, an aspirin-like compound. Intravenous infusion of vitamin C, a potent antioxidant, will be used to determine the effects of oxidative stress on EDD. Additional insight into the cellular and molecular mechanisms involved in age- and exercise-related effects on EDD will be obtained by measurement of circulating markers of inflammation and oxidative stress and gene and/or protein expression of inflammatory molecules, oxidatively modified proteins, and oxidant and antioxidant enzymes in peripheral blood mononuclear cells and vascular endothelial cells from human subjects. The proposed research project has important public health relevance as CVD remains a leading cause of illness and death in the US.

描述（由申请人提供）：这个博士前NRSA的建议寻求在新兴的，生物医学上重要的领域“血管老化”的研究职业发展的支持。候选人步行者女士的职业目标是成为转化研究的独立调查员，重点是介导人类血管衰老的机制和预防或逆转血管衰老的干预措施。该研究项目对预防心血管疾病（CVD）具有重要的临床意义，因为血管老化现在被认为是CVD的主要危险因素。该项目将重点关注血管内皮功能的降低，这是血管老化的关键表现，通过测量内皮依赖性舒张（EDO）来确定。EDD随着年龄的增长而明显减少，即使在健康的老年人中也是如此，但其潜在机制尚未完全了解。慢性低度炎症（与氧化应激相关）是一种尚未直接研究的可能机制。与久坐不动的同龄人相比，定期进行有氧运动的老年人在很大程度上保留了EDD。目前尚不清楚，如果没有炎症和相关的氧化应激介导的抑制EDD有助于保存功能习惯性行使老年人。炎症和氧化应激对衰老和年龄相关疾病的影响是国家衰老研究所的主要研究目标。为了研究这些主题，将研究年轻和老年健康久坐和习惯锻炼的男性和女性。炎症对EDD（肱动脉血流介导的扩张）的影响将通过口服水杨酸（一种阿司匹林样化合物）对核因子κ B信号传导的短期抑制来确定。静脉输注维生素C，一种有效的抗氧化剂，将用于确定氧化应激对EDD的影响。通过测量受试者外周血单核细胞和血管内皮细胞中炎症和氧化应激的循环标志物、炎症分子的基因和/或蛋白质表达、氧化修饰蛋白、氧化剂和抗氧化酶，将进一步深入了解与年龄和运动相关的EDD效应相关的细胞和分子机制。拟议的研究项目具有重要的公共卫生相关性，因为CVD仍然是美国疾病和死亡的主要原因。