Study of the role of secreted platelet thiol isomerases in the regulation of platelet function, haemostasis & thrombosis

血小板是一种微小的血细胞，其作用是在损伤过程中血管破裂时触发血液凝结。虽然这显然对于防止过度和危及生命的出血是必不可少的，但对血液凝结的异常刺激可能是灾难性的，特别是如果这导致动脉或静脉内的血液凝结。这是一种被称为血栓形成的情况，当这种情况发生在为心肌提供血液的动脉时，可能会导致心脏病发作。血栓形成也通常发生在为大脑提供血液的血管中，在这种情况下，它会导致中风。这两种情况在英国都很常见，而且往往是致命的。在这些情况下，血栓形成的原因通常是潜在的疾病，如血管壁上形成的脂肪病变，容易破裂，但血小板是触发危险血栓形成的最终责任。在预防血栓形成方面，使用药物抑制血小板的反应在许多有风险的患者中取得了成功，尽管许多患者没有获得任何好处，甚至可能遭受出血等副作用。为了开发更好的针对血小板以预防血栓形成的药物，科学家需要更多地了解血小板如何识别损伤，然后刺激血液凝结。在这个研究项目中，我们将研究一些我们已经发现的当血小板遇到组织损伤时释放的蛋白质。我们知道，一旦释放，这些分子中的一些会附着在血小板表面，以某种方式增强血小板的凝血活性。这项研究的目的是找出释放的哪些蛋白质对控制血小板及其工作方式是重要的。我们还将使用新的实验程序来确定这些分子是否会导致血栓形成。预计这个项目将使我们对血小板如何调节其功能和相关分子的鉴定有一个新的理解。在未来的研究中，这一知识可能会导致开发更有效的药物来成功地预防血栓形成。

Platelets are tiny blood cells whose role is to trigger the blood to clot when blood vessels become ruptured during injury. While this is clearly essential to prevent excessive and life-threatening bleeding, abnormal stimulation of blood clotting can be catastrophic, particularly if this leads to the clotting of blood within an artery or vein. This is a condition know as thrombosis, and when this happens in arteries that supply the heart muscle with blood it can cause a heart attack. Thrombosis also commonly occurs in the blood vessels that supply the brain with blood, and in this case it causes strokes. Both of these conditions are very common in the UK and are frequently fatal. The cause of thrombosis in these situations is often underlying diseases such as the formation of fatty lesions in the wall of blood vessels that are liable to rupture, but platelets are ultimately responsible for triggering a dangerous clot to form. The use of drugs to dampen down the responses of platelets has been successful in many ‘at risk’ patients in the prevention of thrombosis, although many patients gain no benefit and may even suffer side effects such as bleeding. In order to develop better drugs that target platelets to prevent thrombosis, scientists need to know more about how platelets recognise injury, and then stimulate the blood to clot. In this research project we will investigate some proteins that we have found to be released by platelets when they encounter tissue injury. We know that once released some of these molecules attach themselves to the platelet surface and somehow enhance the platelet clotting activity. The purpose of this study is to work out which of the proteins that are released are important to control platelets and how they work. We will also determine whether these molecules contribute to thrombosis using new experimental procedures. It is anticipated that this project will equip us with a new understanding of how platelets regulate their functions and the identification of the molecules involved. This knowledge may lead, in future studies, to the development of more effective drugs to successfully prevent thrombosis.