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
- 来源:
- 关键词:AcuteAcute Lung InjuryAcute Respiratory Distress SyndromeAffectAgonistAnimal GeneticsAnimal ModelAreaBacteriaBindingBiochemicalBlood VesselsBrain EdemaCause of DeathCell DeathCell Death InductionCell NucleusCellsCessation of lifeCirculationComplexDNA-Binding ProteinsDataDevelopmentDoseEndothelial CellsEndotheliumFailureFosteringFunctional disorderGenetic ModelsHealthHistonesImmuneInfectionInflammationInflammatoryInjuryInvestigationKnowledgeLipidsLungMediatingMembrane LipidsMembrane MicrodomainsMicrocirculationModelingMolecularMolecular TargetMultiple Organ FailureNF-kappa BNecrosisNuclearOperative Surgical ProceduresOrganOrgan failureParticulate MatterPathologicPathway interactionsPatientsPatternPeptidesPermeabilityPilot ProjectsPlayPrognostic FactorPublishingPulmonary EdemaReceptor CellRegulationSepsisSeveritiesSignal TransductionStaphylococcus aureusStimulusSurfaceSyndromeTNFRSF10B geneTestingTissuesToxinTraumaTraumatic injuryVascular DiseasesVascular Endothelial CellVascular EndotheliumVascular Permeabilitiescell injuryendothelial dysfunctionextracellularimaging approachimprovedinjuredinsightlung injurymortalitynovelnovel therapeutic interventionpathogenic bacteriareceptorrecruitrespiratoryresponsescavenger receptortissue injurytraffickingtranslational studyvascular inflammation
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.
细胞外组蛋白引起微血管内皮细胞损伤的机制
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:
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