Flow regulation of the Alk1/Eng pathway in vascular homeostasis and disease
Alk1/Eng 通路在血管稳态和疾病中的流量调节
基本信息
- 批准号:10718429
- 负责人:
- 金额:$ 77.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-15 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultArteriesArteriovenous malformationBindingBiologicalBlood VesselsBlood flowCRISPR screenCell Cycle ArrestCell Surface ReceptorsComplexCoronaryDataDevelopmentDiameterDiseaseEmbryoEmbryonic DevelopmentEndoglinEndothelial CellsFailureGene ExpressionGenesGeneticHereditary hemorrhagic telangiectasiaHomeostasisHumanImpairmentInflammatoryKDR geneKnowledgeLifeLigandsLinkLiquid substanceMediatingMediatorMolecularMusPIK3CG genePathologicPathway interactionsPatientsPerfusionPericytesPeripheral arterial diseasePhysiologicalPiezo 1 ion channelPreventionRegulationReportingRoleSamplingSignal PathwaySignal TransductionTestingTissuesVascular Endothelial CellVascular remodelingZebrafishhemodynamicsimprovedimproved outcomein vivoinhibitorinsightloss of functionmalformationmechanotransductionmitochondrial metabolismmouse modelmutantnovelprogramsreceptorrecruitresponseshear stresssingle-cell RNA sequencingtherapeutic evaluationtherapeutic targetwhole genome
项目摘要
PROJECT SUMMARY
Fluid shear stress-dependent vessel remodeling is an essential regulatory mechanism in embryonic
development and in adult vascular homeostasis where it optimizes blood flow to target tissues. Conversely, un-
or mis-regulated remodeling results in vascular malformations, while poor remodeling is a key aspect of blood
flow restriction in coronary and periphery artery disease. Our preliminary data reveal the existence of a regulatory
network with two mutually inhibitory states, one associated with vessel stability and one with physiological
outward remodeling or pathological AVM formation. These results allow us to propose a unifying hypothesis that
links physiological and pathological remodeling, and suggest the existence of control points that can be
manipulated to either increase or decrease vascular lumen diameter. The project aims to elucidate these
regulatory mechanisms and then harness these new insights to investigate their relevance to vascular
development, to identify therapeutic targets for HHT patients who suffer from excessive pathological remodeling,
and identify therapeutic targets for coronary and peripheral artery disease patients where physiological
remodeling is impaired. We will define the molecular basis of this novel EC shear stress mechanism, determine
its biological role and develop and test therapeutic applications based on this knowledge.
项目摘要
流体切应力依赖性血管重构是胚胎发育的重要调控机制
在发育和成人血管稳态中,它优化了流向靶组织的血流。相反,联合国-
或失调的重塑导致血管畸形,而不良重塑是血液流变学的一个关键方面,
冠状动脉和外周动脉疾病中的血流限制。我们的初步数据显示,
具有两个相互抑制状态的网络,一个与血管稳定性相关,另一个与生理性相关。
向外重塑或病理性AVM形成。这些结果使我们能够提出一个统一的假设,
连接生理和病理重塑,并建议存在控制点,可以
操纵以增加或减小血管腔直径。该项目旨在阐明这些
调节机制,然后利用这些新的见解来研究它们与血管
开发,以确定患有过度病理性重塑的HHT患者的治疗靶点,
并确定冠状动脉和外周动脉疾病患者的治疗靶点,
重塑受损。我们将定义这种新型EC剪切应力机制的分子基础,确定
它的生物学作用,并开发和测试基于这一知识的治疗应用。
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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Anne Christine Eichmann其他文献
Anne Christine Eichmann的其他文献
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{{ truncateString('Anne Christine Eichmann', 18)}}的其他基金
Role of meningeal lymphatic vasculature in neuroimmune communication development
脑膜淋巴管系统在神经免疫通讯发育中的作用
- 批准号:
10566682 - 财政年份:2023
- 资助金额:
$ 77.56万 - 项目类别:
Dynamic control of vascular permeability in development and disease
发育和疾病过程中血管通透性的动态控制
- 批准号:
9977245 - 财政年份:2019
- 资助金额:
$ 77.56万 - 项目类别:
Dynamic control of vascular permeability in development and disease
发育和疾病过程中血管通透性的动态控制
- 批准号:
10207760 - 财政年份:2019
- 资助金额:
$ 77.56万 - 项目类别:
Dynamic control of vascular permeability in development and disease
发育和疾病过程中血管通透性的动态控制
- 批准号:
10421063 - 财政年份:2019
- 资助金额:
$ 77.56万 - 项目类别:
Novel approached to prevent diet-induced obesity via lacteal junctions
通过乳腺连接预防饮食引起的肥胖的新方法
- 批准号:
10394841 - 财政年份:2019
- 资助金额:
$ 77.56万 - 项目类别:
Novel approaches to manipulate sprouting angiogenesis
操纵萌芽血管生成的新方法
- 批准号:
9313892 - 财政年份:2015
- 资助金额:
$ 77.56万 - 项目类别:
Slit2-ROBO signaling in pericytes and myeloid cells controls vascular development and ocular neovascular disease
周细胞和骨髓细胞中的 Slit2-ROBO 信号控制血管发育和眼部新生血管疾病
- 批准号:
10363427 - 财政年份:2015
- 资助金额:
$ 77.56万 - 项目类别:
Slit2-ROBO signaling in pericytes and myeloid cells controls vascular development and ocular neovascular disease
周细胞和骨髓细胞中的 Slit2-ROBO 信号控制血管发育和眼部新生血管疾病
- 批准号:
10565897 - 财政年份:2015
- 资助金额:
$ 77.56万 - 项目类别:
Targeting endothelial migration to prevent neovascularization
靶向内皮迁移以预防新血管形成
- 批准号:
9099868 - 财政年份:2015
- 资助金额:
$ 77.56万 - 项目类别:
Targeting endothelial migration to prevent neovascularization
靶向内皮迁移以预防新血管形成
- 批准号:
9260074 - 财政年份:2015
- 资助金额:
$ 77.56万 - 项目类别:
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