血小板整合素αIIbβ3通过inside-out和outside-in信号通路在血小板聚集、血栓形成和动脉粥样硬化（AS）中起关键作用。辅酶Q10具有多种生物活性可防治多种慢性代谢性疾病。我们以往研究表明，服用辅酶Q10可抑制高脂血症患者血小板聚集和αIIbβ3的活化，并在体外抑制其outside-in通路，但辅酶Q10对糖脂紊乱患者血小板αIIbβ3的体内外效应及调控机制缺乏研究。本项目将开展以下研究：1）在体外探讨辅酶Q10对糖脂代谢紊乱患者血小板αIIbβ3及其信号通路Syk/Erk/JNK、PI3K/PDK/GSk3β等的作用和调控；2）在糖脂代谢紊乱人群，研究补充辅酶Q10对血小板αIIbβ3功能及其通路的影响；3）用ApoE-/-小鼠明确辅酶Q10经血小板αIIbβ3调控AS形成的效应。研究将首次阐明血小板αIIbβ3分子作为辅酶Q10改善糖脂代谢的新靶点和分子机制。

Platelet integrin αIIbβ3 plays a crucial important role in platelet aggregation, thrombosis formation and atherosclerosis development. Initiating the inside-out signaling events lead to integrin αIIbβ3 activation, and the αIIbβ3 outside-in signaling drives processes of platelet spreading, stable thrombus formation, and clot retraction. Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. There are lots of chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate their symptoms and/or retard the onset of these diseases. In the applicant’s lab, we have found that CoQ10 exerts its anti-atherosclerosis effect through the nuclear receptor signaling pathway that affects the reverse translocation of cholesterol in macrophages. Recently, we have also found that CoQ10 significantly inhibited the activation of platelet αIIbβ3 in patients with hyperlipidemia and inhibits its outside-in signaling pathway in vitro, however, there is no any reports or studies on the improvement and mechanisms of CoQ10 on the disorder of glucose and lipid homeostasis through platelet integrin αIIbβ3 pathway until now. Therefore, we will observe the effects of CoQ10 on the purified platelet αIIbβ3 in patients with the disorder of glucose and lipid homeostasis, and explore the regulation of CoQ10 on key proteins of the inside-out and outside-in signaling pathways in vitro, such as Syk/PKC/Erk1/2 /JNK and PI3K/PDK/Akt/ GSk3β. Besides, we will study the effects of CoQ10 on platelet αIIbβ3 molecule and its pathway in patients with the disorder of glucose and lipid homeostasis in vivo. Furthermore, the ApoE-/- mice will be used to determine the influence of platelet αIIbβ3 on the formation and development of atherosclerosis. This study will clarify the platelet integrin αIIbβ3 molecules as a new target for preventing and treating the disorder of glucose and lipid homeostasis by CoQ10 and the corresponding molecular mechanisms in the cells, animals and population levels.