Initiation and Regulation of Platelet Thrombus Formation
血小板血栓形成的引发和调节
基本信息
- 批准号:6968162
- 负责人:
- 金额:$ 51.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-12-01 至 2009-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The purpose of this application is to study the role played by van Willebrand factor (VWF) in initiating platelet deposition at sites of vascular injury, particularly in areas of the circulation characterized by rapid blood flow. The goal is to elucidate the mechanisms of adhesive interactions and cellular responses that are relevant to the arrest of bleeding from wounded tissues but also to the development of common and serious diseases caused by arterial thrombosis, such as myocardial infarction and stroke. The first aim is to define the
biomechanical characteristics of the bonds formed between the VWF A1 domain and the platelet
ilycoprotein (GP) Ib-alpha in relation to specific structural aspects of the A1 domain. The second aim is to define the mechanisms through which soluble VWF multimers and membrane tethers contribute to stabilizing platelet adhesion mediated by GP Ib-alpha. The third aim is based on structural evidence that alpha-thrombin may stabilize the VWF A1 domain-GP Ib-alpha interaction, and may thus play an unexpected role in modulating the initial adhesion of platelets to a thrombogenic surface through a mechanism that is independent of platelet activation. The proposed studies will clarify the biological significance and mechanism of this novel athrombin
function. The fourth aim is to characterize the signaling events related to the interaction between
the VWF A1 domain and GP Ib-alpha, and obtain a more definitive definition of the mechanisms through which the interaction contributes to platelet activation. The fifth aim is to define how VWF binds to extracellular matrix components, in particular to define the potential biological significance of the interactions with collagen type VI and the oligosaccharides that are present in proteoglycans. Extensive interactions with all the other projects in the program and with a core A will facilitate the development of these aims. The results of the proposed studies will have an impact on public health by providing novel mechanistic information on processes that are central to normal hemostasis and pathological arterial thrombosis.
本申请的目的是研究货车维勒布兰德因子(VWF)在血管损伤部位,特别是在以快速血流为特征的循环区域中引发血小板沉积中所起的作用。目的是阐明粘附相互作用和细胞反应的机制,这些机制与阻止受伤组织出血有关,也与动脉血栓形成引起的常见和严重疾病(如心肌梗死和中风)的发展有关。第一个目标是定义
VWF A1结构域与血小板结合的生物力学特性
糖蛋白(GP)Ib-α与A1结构域的特定结构方面的关系。第二个目的是确定可溶性VWF多聚体和膜系链有助于稳定GP Ib-α介导的血小板粘附的机制。第三个目的是基于结构证据,即α-凝血酶可以稳定VWF A1结构域-GP Ib-α相互作用,因此可以通过独立于血小板活化的机制在调节血小板与血栓形成表面的初始粘附中发挥意想不到的作用。这些研究将有助于阐明这种新型凝血酶的生物学意义和作用机制
功能第四个目标是表征与以下之间的相互作用相关的信号事件:
的VWF A1域和GP Ib-α,并获得一个更明确的定义的机制,通过这种相互作用有助于血小板活化。第五个目的是确定VWF如何与细胞外基质成分结合,特别是确定与VI型胶原和蛋白聚糖中存在的寡糖相互作用的潜在生物学意义。与该计划中的所有其他项目以及核心A的广泛互动将促进这些目标的发展。拟议研究的结果将通过提供关于正常止血和病理性动脉血栓形成的核心过程的新机制信息,对公共卫生产生影响。
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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Zaverio M Ruggeri其他文献
Pathogen Reduced Cryoprecipitated Fibrinogen Complex (IFC) and Cryoprecipitated AHF Contain Von Willebrand Factor with Comparable Binding to Collagen and Support Shear-Induced Platelet Thrombus Formation
- DOI:
10.1182/blood-2023-187124 - 发表时间:
2023-11-02 - 期刊:
- 影响因子:
- 作者:
Subramanian Yegneswaran;Alessandro Zarpellon;Jennifer N Orje;Michelle Gatmaitan;Nina Mufti;Laurence Corash;Zaverio M Ruggeri - 通讯作者:
Zaverio M Ruggeri
Neutrophils release brakes of coagulation
中性粒细胞释放凝血的抑制物
- DOI:
10.1038/nm0810-851 - 发表时间:
2010-08-01 - 期刊:
- 影响因子:50.000
- 作者:
Wolfram Ruf;Zaverio M Ruggeri - 通讯作者:
Zaverio M Ruggeri
Zaverio M Ruggeri的其他文献
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{{ truncateString('Zaverio M Ruggeri', 18)}}的其他基金
Glycoprotein Ib in vascular biology and host defense
糖蛋白 Ib 在血管生物学和宿主防御中的作用
- 批准号:
9384693 - 财政年份:2017
- 资助金额:
$ 51.72万 - 项目类别:
Platelet and coagulation activation in response to vascular injury
响应血管损伤的血小板和凝血激活
- 批准号:
9198882 - 财政年份:2014
- 资助金额:
$ 51.72万 - 项目类别:
Platelet and coagulation activation in response to vascular injury
响应血管损伤的血小板和凝血激活
- 批准号:
8976235 - 财政年份:2014
- 资助金额:
$ 51.72万 - 项目类别:
Role of Von Willebrand Factor in Platelet Thrombosis Formation
血管性血友病因子在血小板血栓形成中的作用
- 批准号:
8256550 - 财政年份:2011
- 资助金额:
$ 51.72万 - 项目类别:
Role of Von Willebrand Factor in Platelet Thrombosis Formation
血管性血友病因子在血小板血栓形成中的作用
- 批准号:
7995814 - 财政年份:2010
- 资助金额:
$ 51.72万 - 项目类别:
Role of von Willebrand Factor in Platelet Thrombus Formation
血管性血友病因子在血小板血栓形成中的作用
- 批准号:
7768171 - 财政年份:2009
- 资助金额:
$ 51.72万 - 项目类别:
Ex Vivo and In Vivo Models of Hemostasis and Thrombosis Core
止血和血栓核心的体外和体内模型
- 批准号:
7029350 - 财政年份:2005
- 资助金额:
$ 51.72万 - 项目类别:
Platelet Interactions with Vessel Wall Components
血小板与血管壁成分的相互作用
- 批准号:
7029340 - 财政年份:2005
- 资助金额:
$ 51.72万 - 项目类别:
Platelet interactions with vessel wall components
血小板与血管壁成分的相互作用
- 批准号:
6852337 - 财政年份:2004
- 资助金额:
$ 51.72万 - 项目类别:
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