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，它的作用是在受伤时血管破裂时触发血液凝结。虽然这对于防止过度出血和危及生命的出血显然是必不可少的，但异常刺激血液凝固可能是灾难性的，特别是如果这导致动脉或静脉内的血液凝固。这种情况被称为血栓形成，当这种情况发生在为心肌供血的动脉中时，就会导致心脏病发作。血栓形成也经常发生在为大脑供血的血管中，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，如血管壁中容易破裂的脂肪病变的形成，但血小板最终是触发危险凝块形成的原因。在预防血栓形成方面，使用药物抑制血小板反应已在许多“高危”患者中取得成功，尽管许多患者没有获益，甚至可能出现出血等副作用。为了开发针对血小板的更好的药物来预防血栓形成，科学家们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，我们将研究我们发现的血小板在遇到组织损伤时释放的一些蛋白质。我们知道，一旦这些分子被释放，它们就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很重要，以及它们是如何起作用的。我们还将确定这些分子是否有助于血栓形成使用新的实验程序。预计该项目将使我们对血小板如何调节其功能和识别所涉及的分子有新的认识。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.