Role of platelets in regulating fibrinolysis

血小板在调节纤维蛋白溶解中的作用

• 批准号: 371957-2010
• 负责人: Boffa, Michael
• 金额: $ 2.4万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572850
• 关键词: Role; platelets; regulating; fibrinolysis

Upon injury to a blood vessel, a blood clot forms at the site of injury to prevent catastrophic loss of blood. When repair to the tissue has ensued, the blood clot is removed by a system called the fibrinolytic system. The balance between blood clot formation (coagulation) and blood clot breakdown (fibrinolysis) is crucial, as imbalances can lead to clotting disorders such as heart attacks and strokes or to bleeding disorders such as hemophilia. Our research concerns platelets, which are cell fragments that circulate in the blood and are essential for proper blood clot formation. They are responsible for the first plug at the wound site, and they help to coordinate the blood clotting process. Specifically, we are interesting in the role that platelets play in coordinating the balance between blood clot formation and breakdown. Our current focus is a protein called TAFI (thrombin-activatable fibrinolysis inhibitor) which helps to regulate this balance. It was once thought that TAFI was only present in plasma, which is the fluid portion of blood. However, it appears that there is also a distinct portion of TAFI within the platelet that can be released when platelets become activated at the site of injury. No one knows what the purpose of this platelet form of TAFI is, or if it is different in its properties from plasma TAFI. We propose to answer these questions. First we will try and isolate platelet TAFI in pure form. From there, we can study its characteristics and compare them to those of plasma TAFI. Next, we will assess if platelet TAFI affects the attachment of platelets to injured blood vessel walls and the subsequent formation and breakdown of blood clots. We will do this both in model vessels in test tubes or in mice in which we have specifically deleted either platelet or plasma TAFI. Our studies will provide important new information on how blood clotting and blood clot breakdown are regulated.

血管损伤后，损伤部位会形成血块，以防止灾难性的失血。当组织修复完成后，血液凝块被称为纤溶系统的系统清除。血液凝块形成(凝血)和血液凝块破裂(纤溶)之间的平衡至关重要，因为失衡可能导致心脏病发作和中风等凝血障碍或血友病等出血性疾病。我们的研究涉及到血小板，它是在血液中循环的细胞碎片，对于正常的血液凝块形成是必不可少的。它们负责伤口处的第一个塞子，并帮助协调血液凝结过程。具体地说，我们感兴趣的是血小板在协调血液凝块形成和破裂之间的平衡方面所起的作用。我们目前的重点是一种名为TAFI(凝血酶激活的纤溶抑制物)的蛋白质，它有助于调节这种平衡。曾经认为TAFI只存在于血浆中，血浆是血液中的液体部分。然而，当损伤部位的血小板被激活时，似乎在血小板内也有明显的TAFI部分被释放。没有人知道这种血小板形式的TAFI的用途是什么，或者它的性质是否与血浆TAFI不同。我们建议回答这些问题。首先，我们将尝试以纯形式分离血小板Tafi。从那里，我们可以研究它的特性，并将其与血浆TAFI的特性进行比较。接下来，我们将评估血小板TAFI是否影响血小板与受损血管壁的附着以及随后血栓的形成和破裂。我们将在试管中的模型血管中或在我们特别删除了血小板或血浆TAFI的小鼠中进行这项研究。我们的研究将为如何调节血液凝结和血栓破裂提供重要的新信息。