动脉血栓性疾病如心肌梗死危害巨大。动脉血栓形成过程复杂，关键细胞血小板活化机制多样，高血栓风险患者需服用至少2类抗血小板药物协同作用和药物抵抗等现象，均提示研究血小板活化机制仍具有重要价值。血小板能量代谢主要在线粒体进行，后者决定了血小板的形态、功能以及活化、聚集活性。酰基甘油激酶(AGK)是一种维持线粒体稳态的关键激酶。申请人前期研究发现，AGK在人和小鼠血小板高表达；特异缺失AGK能明显压制胶原诱导的血小板活化。有趣的是尽管G126E点突变能使AGK丧失激酶活性，但对胶原诱导的血小板活化却无明显影响。机制研究发现AGK缺失能造成血小板线粒体呼吸链复合体I缺失。因此我们提出AGK是血小板线粒体呼吸链复合体I形成的关键调控蛋白，可能在血小板活化和动脉血栓形成过程中发挥重要作用。在本申请中我们将利用转基因动物模型及多种技术，针对AGK调控机制展开研究，为研制新型抗血小板药物提供重要理论依据。

Arterial thrombotic diseases such as myocardial infarction are extremely harmful. The arterial thrombosis process is complicated, and the key cell platelet activation mechanism is diverse. Patients with high thrombosis risk require at least two antiplatelet drugs synergistic effects and drug resistance, all of which suggest that the study of platelet activation mechanism is still of great value. Platelet energy metabolism occurs in mitochondria predominantly, which determines the morphology, function, and activation and aggregation activities of platelets. Acylglycerol kinase (AGK) is a critical kinase that maintains mitochondrial homeostasis. Our previous studies have shown that AGK is highly expressed in human and mouse platelets, and specific knock out of AGK can significantly suppress collagen-induced platelet activation. Interestingly, although G126E point mutations can cause AGK to lose kinase activity, it has no significant effect on collagen-induced platelet activation. Mechanism studies have found that AGK deletion can cause the loss of platelet mitochondrial respiratory chain complex I. Therefore, it is hypothesized in our study that AGK is a key regulatory protein for the formation of platelet mitochondrial respiratory chain complex I, which may play an essential role in platelet activation and arterial thrombosis. In this application, transgenic animal models and a variety of techniques will be utilized to conduct research on specific regulatory mechanisms, which will provide an important theoretical basis for the development of new antiplatelet drugs.