缺氧促进心肌细胞exosome分泌介导miR-22调控血管新生的作用机制

项目名称： 缺氧促进心肌细胞exosome分泌介导miR-22调控血管新生的作用机制

项目编号： No.81470592

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： 王国坤

作者单位： 中国人民解放军第二军医大学

项目金额： 73万元

中文摘要： 血管新生是微血管发展成血流供应系统的生理过程，是缺血性心脏病恢复治疗的重要方向。外泌体(exosome)介导的细胞间信号传递是国际研究的前沿。最新研究发现miRNA经exosome传递可调控靶细胞功能，参与调节血管新生、炎症反应等生理病理进程。我们前期发现缺氧刺激心肌细胞分泌的exosome对内皮细胞的生长及血管新生具有调节作用，miRNA芯片显示缺氧刺激引起心肌细胞exosome内容物中miR-22明显升高，内皮细胞过表达miR-22可促进细胞增殖和迁移。基于此提出科学假说：缺氧刺激促进心肌细胞分泌miR-22，经exosome介导调控血管新生。我们拟通过对GFP转基因心肌细胞exosome示踪定位，确定其介导心肌细胞与内皮细胞间信息传递；通过miR-22靶基因确认和相关信号通路的变化，阐明miR-22调控血管新生的机制。研究结果将对缺血性心脏病的治疗和术后恢复提供新的策略和研究方向。

中文关键词： 外泌体；心肌细胞；血管新生；缺氧；miR-22

英文摘要： Angiogenesis, the physiological processes of microvascular developing to the circulating supply system, is an important direction for ischemic heart disease therapy and recovery. Signal transmission between cells mediated by exosome had become as forefront of international research. Recent study found that miRNA could regulate function of targeted cells mediated by exosome, and be involved in regulating physiological and pathological processes, such as angiogenesis and inflammation. Our previous study had discovered that cardiomyocytes exosome secreted increased by hypoxic stimulation, and had regulation roles on endothelial cell growth and angiogenesis. MiR-22 was identified as the most obvious change miRNA in cardiomyocytes exosome contents stimulated by hypoxia from miRNA microarray assay. Moreover, miR-22 overexpression in endothelial cells could promote cell proliferation and migration. Therefore, the scientific hypothesis was proposed: Cardiomyocytes-derived miR-22 regulated angiogenesis mediated by hypoxia-induced exosome. We intend to determine exosome mediating message transfering between cardiomyocytes and endothelial cells though GFP transgenic cardiomyocytes-derived exosome trace and location, to clarify the mechanism of miR-22 regulating angiogenesis by identifing targeted gene and signaling pathway. The results will provide novel therapy strategies and research direction for ischemic heart disease.

英文关键词： Exosome;Cardiac myocyte;Angiogenesis;Hypoxia;miR-22