miR-223调控血小板活化在动脉粥样硬化中的作用及机制研究

项目名称： miR-223调控血小板活化在动脉粥样硬化中的作用及机制研究

项目编号： No.81500332

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 曾小莉

作者单位： 首都医科大学

项目金额： 18万元

中文摘要： 近年来，与血小板活化相关的微小RNA表达成为动脉粥样硬化（AS）研究的新视点。我们前期研究发现冠心病患者血小板miR-223表达增高，其水平与血小板活化相关，结果提示miR-223调控血小板活化在AS发生发展中可能发挥重要作用。为此，我们将通过血小板、血管内皮细胞和AS动物模型，从分子、细胞、整体、临床四个水平研究miR-223调控血小板活化在AS中的作用，探讨miR-223与靶基因的相互作用在AS发生中的作用机制。细胞水平观察miR-223对血小板活化，对血小板与血管内皮细胞黏附的生物学作用及其机制；整体水平观察直接AS小鼠体内注射经miR-223处理的血小板能否延缓AS病理进程；临床水平观察miR-223与冠心病患者血小板活化因子的关系。本研究将从与血小板活化相关的miR-223特异性表达这个新视角，为揭示血小板活化在AS发生中的作用机理奠定基础，为AS防治提供新的治疗靶点和研究方向。

中文关键词： 动脉粥样硬化；微小RNA-223；血小板；血管内皮细胞

英文摘要： Platelets are involved in vascular homeostasis and inflammation through interaction with circulating blood cells and vascular wall. MicroRNAs (miRNAs) are small, conserved and non-coding RNA molecules, which interact directly with specific mRNAs regions regulating gene expression. In recent years, the specific expressions of miRNAs related to platelet activation have become a new viewpoint of atherosclerosis research. Our previous studies have found that miR-223, expressed highly in platelets of the patients with coronary heart disease (CHD), was remarkably correlated with the platelet activation. The results have indicated that the platelet activation regulated by miR-223 may play a novel role in the development of atherosclerosis. Therefore, we will study the role of in platelet activation and atherosclerosis from molecular, cellular, organic, clinical aspects through platelets, vascular endothelial cells and atherosclerosis animal model. Furthermore, we will study the interaction of miR-223 and target genes in atherosclerosis and its mechanism. Firstly, we will study the biological effects of miR-223 on platelet activation, interaction of platelet to endothelial cells and its mechanism from cellular level. Secondly, we will observe whether platelet treated with miR-223 would slow the pathological process of atherosclerosis in atherosclerosis model mouse from organic level. Finally, we will observe the expression change of miR-223 in platelet of patients with coronary heart disease from clinical level. In summary, this study will offer a new therapeutic target and direction for prevention and cure of atherosclerosis; will lay a foundation of revealing the mechanism of platelet activation in atherosclerosis from a new perspective of miR-223 expression related to platelet activation; will provide a new idea for prevention, early diagnosis and treatment of atherosclerosis related diseases.

英文关键词： atherosclerosis;microRNA-223;platelet;vascular endothelial cell