Reduced Inflammatory Suppression of EDD with Habitual Exercise in Older Adults

通过老年人的习惯性运动减少 EDD 的炎症抑制

基本信息

  • 批准号:
    7928377
  • 负责人:
  • 金额:
    $ 48.51万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-01 至 2011-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This amended application seeks support for new work aimed at the treatment of vascular aging in humans. The proposed research will determine if habitual aerobic exercise improves endothelium-dependent dilation (EDD), a clinically important marker of vascular endothelial function and cardiovascular disease risk, in middle- aged/older adults by reducing tonic inflammation- and oxidative stress-mediated suppression of EDD. The proposed work also will provide novel insight into the cellular and molecular mechanisms by which regular aerobic exercise may improve tonic inflammation- and oxidative stress-mediated suppression of EDD. Integrative Working Hypothesis: In previously sedentary healthy middle-aged/older (60-79 years) men and women, the improvements in EDD in response to habitual aerobic exercise will be associated with reduced tonic inflammation-mediated suppression of EDD. The latter will, in turn, be related to: 7 a reduced systemic pro-inflammatory "milieu", characterized by decreased pro-inflammatory/increased anti-inflammatory plasma concentrations of cytokines and other inflammatory mediators 7 a reduced inflammatory vascular endothelial phenotype, characterized by decreased pro-inflammatory/ increased anti-inflammatory cytokine protein expression in the vascular endothelium 7 reduced vascular endothelial activation of the key inflammatory transcription factor, nuclear factor : B (NF:B), associated with changes in the proteins controlling its activation and nuclear translocation. The reduced tonic inflammation-related suppression of EDD will be associated with decreased oxidative stress-mediated inhibition of EDD. The latter will, in turn, be related to: 7 reduced systemic oxidative stress 7 a less pro-oxidant vascular endothelial phenotype, characterized in part by decreased oxidant enzyme and oxidation-modified protein expression in the vascular endothelium. Experimental Approach: We will conduct a 12-week aerobic exercise intervention (randomized design with attention control). The tonic influence of inflammation on EDD will be determined before and after the intervention period by the improvement in EDD in response to short-term blockade of NF:B signaling with orally administered Salsalate. The effects of oxidative stress will be assessed by the increase in EDD in response to acute administration of ascorbic acid (vitamin C), a potent antioxidant. Key outcomes will include brachial artery flow-mediated dilation (EDD) and measures of systemic and/or vascular endothelial inflammation, NF:B-related proteins, oxidative stress, and oxidant and antioxidant enzymes. PUBLIC HEALTH RELEVANCE: This application seeks support for new research aimed at the treatment of aging of the arteries in adults. The proposed research will determine if regular aerobic exercise improves the function of the arteries in middle- aged/older men and women and, if so, if a reduction in the state of inflammation is a major reason for the beneficial effects of exercise.
描述(由申请人提供):本修订申请寻求对旨在治疗人类血管老化的新工作的支持。拟议的研究将确定习惯性有氧运动是否通过减少紧张性炎症和氧化应激介导的EDD抑制来改善中老年人的内皮依赖性舒张(EDD),EDD是血管内皮功能和心血管疾病风险的临床重要标志物。拟议的工作也将提供新的见解,定期有氧运动可能会改善紧张性炎症和氧化应激介导的抑制EDD的细胞和分子机制。综合工作假设:在以前久坐不动的健康中年/老年(60-79岁)男性和女性中,习惯性有氧运动引起的EDD改善与强直性炎症介导的EDD抑制减少相关。后者又将涉及:7.减少的全身促炎“环境”,其特征在于细胞因子和其它炎性介质的促炎/抗炎血浆浓度减少/增加7.减少的炎性血管内皮表型,其特征在于促炎性降低/抗-血管内皮中的炎性细胞因子蛋白表达7降低了关键炎性转录因子核因子:B(NF:B),与控制其活化和核转位的蛋白质的变化有关。紧张性炎症相关的EDD抑制的减少将与氧化应激介导的EDD抑制的减少相关。后者将,反过来,与:7减少全身氧化应激7少促氧化血管内皮表型,其特征在于部分减少氧化酶和氧化修饰的蛋白质在血管内皮的表达。实验方法:我们将进行为期12周的有氧运动干预(注意力控制的随机设计)。在干预期之前和之后,炎症对EDD的紧张性影响将通过EDD响应于口服施用的双水杨酸对NF:B信号传导的短期阻断的改善来确定。氧化应激的影响将通过EDD响应于抗坏血酸(维生素C)(一种有效的抗氧化剂)的急性给药的增加来评估。关键结局将包括肱动脉血流介导的扩张(EDD)和全身和/或血管内皮炎症、NF:B相关蛋白、氧化应激以及氧化剂和抗氧化酶的测量。公共卫生相关性:该申请寻求对旨在治疗成人动脉老化的新研究的支持。这项拟议中的研究将确定定期有氧运动是否能改善中老年男性和女性的动脉功能,如果是的话,炎症状态的减少是否是运动有益效果的主要原因。

项目成果

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DOUGLAS R SEALS其他文献

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{{ truncateString('DOUGLAS R SEALS', 18)}}的其他基金

Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults
被动热疗可降低中年和老年人的收缩压并改善血管功能
  • 批准号:
    10596067
  • 财政年份:
    2022
  • 资助金额:
    $ 48.51万
  • 项目类别:
Targeting cellular senescence to prevent accelerated vascular aging induced by the common chemotherapeutic agent doxorubicin
靶向细胞衰老以防止常见化疗药物阿霉素引起的加速血管老化
  • 批准号:
    10505896
  • 财政年份:
    2022
  • 资助金额:
    $ 48.51万
  • 项目类别:
Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults
被动热疗可降低中年和老年人的收缩压并改善血管功能
  • 批准号:
    10712162
  • 财政年份:
    2022
  • 资助金额:
    $ 48.51万
  • 项目类别:
Targeting cellular senescence to prevent accelerated vascular aging induced by the common chemotherapeutic agent doxorubicin
靶向细胞衰老以防止常见化疗药物阿霉素引起的加速血管老化
  • 批准号:
    10684719
  • 财政年份:
    2022
  • 资助金额:
    $ 48.51万
  • 项目类别:
Passive heat therapy for lowering systolic blood pressure and improving vascular function in mid-life and older adults
被动热疗可降低中年和老年人的收缩压并改善血管功能
  • 批准号:
    10375083
  • 财政年份:
    2022
  • 资助金额:
    $ 48.51万
  • 项目类别:
Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans
线粒体靶向抗氧化剂补充剂可改善人类与年龄相关的血管功能障碍
  • 批准号:
    10538571
  • 财政年份:
    2021
  • 资助金额:
    $ 48.51万
  • 项目类别:
Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with "standard of care" aerobic exercise
用于降低绝经后妇女血压和改善内皮功能的吸气肌力量训练:与“标准护理”有氧运动的比较
  • 批准号:
    10414050
  • 财政年份:
    2021
  • 资助金额:
    $ 48.51万
  • 项目类别:
Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with "standard of care" aerobic exercise
用于降低绝经后妇女血压和改善内皮功能的吸气肌力量训练:与“标准护理”有氧运动的比较
  • 批准号:
    10178631
  • 财政年份:
    2021
  • 资助金额:
    $ 48.51万
  • 项目类别:
Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans
线粒体靶向抗氧化剂补充剂可改善人类与年龄相关的血管功能障碍
  • 批准号:
    10319609
  • 财政年份:
    2021
  • 资助金额:
    $ 48.51万
  • 项目类别:
Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with "standard of care" aerobic exercise
用于降低绝经后妇女血压和改善内皮功能的吸气肌力量训练:与“标准护理”有氧运动的比较
  • 批准号:
    10576933
  • 财政年份:
    2021
  • 资助金额:
    $ 48.51万
  • 项目类别:

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