Mechanisms of airborne particulate matter induced thrombosis

空气颗粒物诱发血栓形成的机制

基本信息

  • 批准号:
    7921554
  • 负责人:
  • 金额:
    $ 37.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-09-01 至 2011-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by the applicant): Ambient participate matter (PM) air pollution contributes significantly to cardiopulmonary morbidity and mortality. There are strong epidemiologic data that link daily levels of ambient PM to hospitalizations for cardiopulmonary disease and daily rates of cardiovascular mortality. Acute exposure to increased levels of PM is also associated with increased risk of acute myocardial infarction, and ischemic stroke. However, the mechanisms by which PM elicits these pathologic events and increases cardiovascular mortality are largely unknown. Exposure of animals and humans to PM alters hemostasis; increasing the levels of fibrinogen, and von Willebrand factor and inducing peripheral arterial thrombosis. In support of a PM-induced prothrombotic state, we have recently observed that exposure of mice to well-characterized PM collected from ambient air in Dusseldorf, Germany caused shortening of the bleeding, prothrombin and partial thromboplastin times, and increased the platelet count and the levels of factor VIII. Moreover, exposure of mice to PM increased bronchoalveolar lavage fluid levels of IL-6, which promotes coagulation and enhances platelet production and thrombin formation. Accordingly, we found that generation of intravascular thrombin was increased 24 hours after exposure to PM. The effect of PM-exposure on thrombin formation was abrogated in mice with targeted deletion of IL-6. Similarly, inhibition of beta-adrenergic receptors, an important regulator of IL-6, attenuated PM-induced thrombin generation. PM-induced stimulation of inflammation and cytokine release has been suggested to be due to the generation of reactive oxygen species (ROS) by epithelial cells and macrophages. These new findings led us to hypothesize that PM causes IL-6 release, which causes a hyper-coagulable state via a ROS-dependent mechanism. To test our hypothesis, we propose to (1) determine whether PM-induced IL-6 production and the resultant hyper-coagulable state are mediated by alveolar macrophages, alveolar epithelial cells, or both, (2) determine whether the PM-induced generation of ROS is required for IL-6 production and the resultant hyper-coagulable state, and (3) determine the role of beta-adrenergic receptors in modulation of the PM-induced IL-6 production and hyper-coagulable state. The studies we are proposing address an important human health problem and could lead to the development of novel therapies to diminish PM-induced cardiovascular events and mortality.
描述(由申请人提供):

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Gokhan M. Mutlu其他文献

Laryngospasm and Paradoxical Bronchoconstriction After Repeated Doses of β<sub>2</sub>- Agonists Containing Edetate Disodium
  • DOI:
    10.4065/75.3.285
  • 发表时间:
    2000-03-01
  • 期刊:
  • 影响因子:
  • 作者:
    Gokhan M. Mutlu;Elizabeth Moonjelly;Lingtak Chan;Christopher O. Olopade
  • 通讯作者:
    Christopher O. Olopade

Gokhan M. Mutlu的其他文献

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{{ truncateString('Gokhan M. Mutlu', 18)}}的其他基金

Mechanisms Underlying Sympathetic Activation-dependent Endothelial Cell Activation by Chronic Intermittent Hypoxia
慢性间歇性缺氧导致交感神经激活依赖性内皮细胞激活的机制
  • 批准号:
    10612099
  • 财政年份:
    2019
  • 资助金额:
    $ 37.64万
  • 项目类别:
Mechanisms Underlying Sympathetic Activation-dependent Endothelial Cell Activation by Chronic Intermittent Hypoxia
慢性间歇性缺氧导致交感神经激活依赖性内皮细胞激活的机制
  • 批准号:
    10409555
  • 财政年份:
    2019
  • 资助金额:
    $ 37.64万
  • 项目类别:
CACHET - Pilot Project
CACHET - 试点项目
  • 批准号:
    10641985
  • 财政年份:
    2017
  • 资助金额:
    $ 37.64万
  • 项目类别:
CACHET - Pilot Project
CACHET - 试点项目
  • 批准号:
    10394646
  • 财政年份:
    2017
  • 资助金额:
    $ 37.64万
  • 项目类别:
Particulate matter-induced changes in DNA methylome and transcriptome
颗粒物诱导的 DNA 甲基化组和转录组变化
  • 批准号:
    9273532
  • 财政年份:
    2016
  • 资助金额:
    $ 37.64万
  • 项目类别:
Particulate matter-induced changes in DNA methylome and transcriptome
颗粒物诱导的 DNA 甲基化组和转录组变化
  • 批准号:
    9098231
  • 财政年份:
    2016
  • 资助金额:
    $ 37.64万
  • 项目类别:
Mechanisms of airborne particulate matter induced thrombosis
空气颗粒物诱发血栓形成的机制
  • 批准号:
    7283020
  • 财政年份:
    2006
  • 资助金额:
    $ 37.64万
  • 项目类别:
Mechanisms of airborne particulate matter induced thrombosis
空气颗粒物诱发血栓形成的机制
  • 批准号:
    7488598
  • 财政年份:
    2006
  • 资助金额:
    $ 37.64万
  • 项目类别:
Role of alveolar macrophages in particulate matter-induced cardiopulmonary disease
肺泡巨噬细胞在颗粒物诱发的心肺疾病中的作用
  • 批准号:
    10163187
  • 财政年份:
    2006
  • 资助金额:
    $ 37.64万
  • 项目类别:
Role of alveolar macrophages in particulate matter-induced cardiopulmonary disease
肺泡巨噬细胞在颗粒物诱发的心肺疾病中的作用
  • 批准号:
    9764366
  • 财政年份:
    2006
  • 资助金额:
    $ 37.64万
  • 项目类别:

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