Mechanisms of microvascular endothelial cell injury caused by extracellular histones

细胞外组蛋白致微血管内皮细胞损伤的机制

基本信息

  • 批准号:
    10679043
  • 负责人:
  • 金额:
    $ 46.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Mechanisms of microvascular endothelial cell injury caused by extracellular histones Abstract Despite the recent progress towards understanding of the basis of increased vascular permeability and inflammation caused by circulating vasoactive peptides, lipids, and exogenous agents (bacteria, toxins, particulate matter), the impact of intracellular compounds released by injured tissues and known as danger- associated molecular patterns (DAMPs) on severity of ongoing acute respiratory syndrome caused by sepsis or traumatic injury remain poorly understood, and molecular mechanisms underlying deleterious effects of DAMPs warrant further investigations. This translational study will investigate effects of nucleus-associated DAMPs, histones, on vascular endothelial function and test a new hypothetical mechanism by which circulating histones target lung microvascular endothelium and worsen lung injury. The central hypothesis tested in this application is that circulating histones elevated during acute lung injury, sepsis, trauma, severe inflammation, or major surgery target vascular endothelium and contribute to overall vascular dysfunction, organ damage and mortality. This may be achieved through: 1) histone-induced engagement of scavenger receptor cluster of differentiation 36 (CD36) leading to propagation of endothelial inflammation and barrier dysfunction; and 2) CD36-induced activation of death signaling by circulating histones contributing to augmentation of ongoing endothelial dysfunction and lung injury. The proposed study may have a broader impact on the other aspects of vascular responses to inflammatory or pro-angiogenic stimuli. Proposed studies will provide mechanistic insights offering better understanding of factors that define severity of sepsis and trauma. These studies may lead to identification of molecular targets and developing new therapeutic approaches to mitigate such deleterious effects of circulating DAMPs.
细胞外组蛋白致微血管内皮细胞损伤的机制 摘要 尽管最近在理解血管通透性增加和 由循环血管活性多肽、脂类和外源性物质(细菌、毒素、 颗粒物),损伤组织释放的细胞内化合物的影响,称为危险- 脓毒症所致持续急性呼吸综合征严重程度的相关分子模式(DAMP) 或创伤性损伤仍然知之甚少,而潜在的有害影响的分子机制 潮湿的情况需要进一步调查。这项翻译研究将调查核相关的影响 组蛋白对血管内皮细胞功能的抑制作用并测试一种新的假想的循环机制 组蛋白以肺微血管内皮细胞为靶点,加重肺损伤。在这里检验的中心假说 应用是在急性肺损伤、脓毒症、创伤、严重炎症、 或大手术以血管内皮细胞为靶点,并导致整体血管功能障碍、器官损害和 死亡率。这可能是通过:1)组蛋白诱导清道夫受体簇参与 分化36(CD36)导致内皮细胞炎症和屏障功能障碍的扩散;以及2) CD36通过循环组蛋白激活死亡信号,有助于增强正在进行的 内皮功能障碍和肺损伤。拟议的研究可能会对其他方面产生更广泛的影响 血管对炎性或促血管生成刺激的反应。拟议的研究将提供机械性的 洞察力提供更好地理解定义脓毒症和创伤严重程度的因素。这些研究可能 导致识别分子靶点并开发新的治疗方法来缓解这种情况 循环潮湿的有害影响。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.
  • DOI:
    10.3389/fphys.2021.758313
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Karki P;Birukova AA
  • 通讯作者:
    Birukova AA
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Anna Birukova其他文献

Anna Birukova的其他文献

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{{ truncateString('Anna Birukova', 18)}}的其他基金

GPR68 as a novel modulator of septic lung injury
GPR68 作为脓毒性肺损伤的新型调节剂
  • 批准号:
    10743219
  • 财政年份:
    2023
  • 资助金额:
    $ 46.56万
  • 项目类别:
Control of septic inflammation and lung microvascular endothelial barrier by cell junction signaling nexus
通过细胞连接信号连接控制化脓性炎症和肺微血管内皮屏障
  • 批准号:
    10207865
  • 财政年份:
    2021
  • 资助金额:
    $ 46.56万
  • 项目类别:
Control of septic inflammation and lung microvascular endothelial barrier by cell junction signaling nexus
通过细胞连接信号连接控制化脓性炎症和肺微血管内皮屏障
  • 批准号:
    10631107
  • 财政年份:
    2021
  • 资助金额:
    $ 46.56万
  • 项目类别:
Control of septic inflammation and lung microvascular endothelial barrier by cell junction signaling nexus
通过细胞连接信号连接控制化脓性炎症和肺微血管内皮屏障
  • 批准号:
    10412071
  • 财政年份:
    2021
  • 资助金额:
    $ 46.56万
  • 项目类别:
Mechanisms of microvascular endothelial cell injury caused by extracellular histones
细胞外组蛋白致微血管内皮细胞损伤的机制
  • 批准号:
    10294004
  • 财政年份:
    2021
  • 资助金额:
    $ 46.56万
  • 项目类别:
Differential mechano-signaling in vascular endothelium by varying degrees of mechanical stretch - Resubmission 01
通过不同程度的机械拉伸在血管内皮中产生差异性机械信号 - 重新提交 01
  • 批准号:
    9167172
  • 财政年份:
    2016
  • 资助金额:
    $ 46.56万
  • 项目类别:
Differential mechano-signaling in vascular endothelium by varying degrees of mechanical stretch - Resubmission 01
通过不同程度的机械拉伸在血管内皮中产生差异性机械信号 - 重新提交 01
  • 批准号:
    9280991
  • 财政年份:
    2016
  • 资助金额:
    $ 46.56万
  • 项目类别:
Differential mechano-signaling in vascular endothelium by varying degrees of mechanical stretch - Resubmission 01
通过不同程度的机械拉伸在血管内皮中产生差异性机械信号 - 重新提交 01
  • 批准号:
    9754858
  • 财政年份:
    2016
  • 资助金额:
    $ 46.56万
  • 项目类别:
Microtubule control of septic inflammation
化脓性炎症的微管控制
  • 批准号:
    8862776
  • 财政年份:
    2015
  • 资助金额:
    $ 46.56万
  • 项目类别:
Microtubule-associated Rac
微管相关Rac
  • 批准号:
    8669123
  • 财政年份:
    2011
  • 资助金额:
    $ 46.56万
  • 项目类别:

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Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8429041
  • 财政年份:
    2011
  • 资助金额:
    $ 46.56万
  • 项目类别:
Analysis of extravascular lung water dynamics and exhaustive evaluation of pulmonary epithelial metabolites to establish a novel therapeutic approach for acute lung injury/ acute respiratory distress syndrome
分析血管外肺水动力学和详尽评估肺上皮代谢物,以建立急性肺损伤/急性呼吸窘迫综合征的新治疗方法
  • 批准号:
    22592023
  • 财政年份:
    2010
  • 资助金额:
    $ 46.56万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
OBSERVATIONAL STUDY OF ACUTE LUNG INJURY & ACUTE RESPIRATORY DISTRESS SYNDROME
急性肺损伤的观察性研究
  • 批准号:
    7603766
  • 财政年份:
    2007
  • 资助金额:
    $ 46.56万
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Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8602427
  • 财政年份:
    2005
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    $ 46.56万
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Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
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    8602351
  • 财政年份:
    2005
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    $ 46.56万
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Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
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    8654999
  • 财政年份:
    2005
  • 资助金额:
    $ 46.56万
  • 项目类别:
Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8844846
  • 财政年份:
    2005
  • 资助金额:
    $ 46.56万
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Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
急性肺损伤和急性呼吸窘迫综合征的治疗
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    8328484
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急性肺损伤和急性呼吸窘迫综合征的治疗
  • 批准号:
    8328493
  • 财政年份:
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急性肺损伤和急性呼吸窘迫综合征的治疗
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    8020428
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