Role of platelets in regulating fibrinolysis

在血管受伤时，在受伤部位形成血凝块，以防止灾难性的失血。当组织修复后，血凝块被称为纤维蛋白溶解系统的系统清除。血凝块形成（凝血）和血凝块分解（纤维蛋白溶解）之间的平衡至关重要，因为失衡可能导致凝血障碍，如心脏病发作和中风或出血性疾病，如血友病。我们的研究涉及血小板，血小板是在血液中循环的细胞碎片，对适当的血凝块形成至关重要。它们负责伤口部位的第一个塞子，并帮助协调血液凝固过程。具体来说，我们感兴趣的是血小板在协调血凝块形成和分解之间的平衡中所起的作用。我们目前的重点是一种称为TAFI（凝血酶激活纤维蛋白溶解抑制剂）的蛋白质，它有助于调节这种平衡。人们曾经认为TAFI只存在于血浆中，血浆是血液的液体部分。然而，当血小板在损伤部位被激活时，血小板内似乎也有一个独特的TAFI部分可以被释放。没有人知道这种血小板形式的TAFI的目的是什么，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，我们将尝试分离纯形式的血小板TAFI。从那里，我们可以研究其特性，并将其与血浆TAFI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的血栓形成和破裂。我们将在试管中的模型血管或小鼠中进行这一研究，其中我们特异性地删除了血小板或血浆TAFI。我们的研究将提供关于如何调节血液凝固和血液凝块分解的重要新信息。

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.