内皮微颗粒携带的microRNA-19b作为细胞间通讯的新信使发挥多靶点调控动脉粥样硬化作用

项目名称： 内皮微颗粒携带的microRNA-19b作为细胞间通讯的新信使发挥多靶点调控动脉粥样硬化作用

项目编号： No.81470473

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈红

作者单位： 北京大学

项目金额： 73万元

中文摘要： 内皮细胞受到刺激后释放微颗粒上携带的物质如microRNA可被运输到受体细胞发挥调节作用，被认为是细胞间通讯的新信使。我们前期发现，不稳定性冠心病患者血液循环微颗粒中microRNA-19b水平明显升高，并且内皮细胞是循环微颗粒中microRNA-19b的来源之一。然而，内皮微颗粒携带的microRNA-19b对动脉粥样硬化（AS）的调控方式和作用机制仍未阐明。本项目拟开展细胞和动物研究，探讨：1、内皮细胞释放的微颗粒中包含有microRNA-19b，2、内皮微颗粒携带的microRNA-19b通过自分泌或旁分泌方式作用于内皮细胞、平滑肌细胞和单核细胞调控AS进程，3、内皮微颗粒携带的microRNA-19b调控AS的分子机制。最终旨在阐明内皮微颗粒携带的microRNA-19b调控AS的细胞间通讯途径、作用靶点和分子机制，为microRNA调控AS提供新的作用方式和机制解释。

中文关键词： 动脉粥样硬化；内皮微颗粒；microRNA-19b；细胞间通讯

英文摘要： Endothelial microparticles (EMPs) are capable of transferring active molecules, such as microRNA, to neighboring cells and regulate the biological functions of these recipient cells, which are considered as the new messengers in cell-cell communication. Our previous study found that microRNA-19b in plasma microparticles of patients with unstable angina was obviously up-regulated, which partially results from the increase of circulating EMPs. Nevertheless, the role of EMPs-mediated transfer of microRNA-19b in atherosclerosis has not yet been elucidated. This present project aims to investigate the following contents: 1. EMPs contain microRNA-19b, 2. EMPs-derived microRNA-19b regulates the progress of atherosclerosis by acting on endothelial cells, smooth muscle cells and monocytes, 3. The mechanism underlies EMPs-derived microRNA-19b in regulating the progressive process of atherosclerosis. The objective of our study is to clarify the molecular mechanism of EMPs-mediated transfer of microRNA-19b into recipient cells involved in atherosclerosis, and to offer a novel regulating manner and explanation for microRNA affecting on the progress of atherosclerosis.

英文关键词： atherosclerosis;endothelial microparticles;microRNA-19b;cell-cell communication