单核细胞端粒酶活性在动脉粥样硬化中的作用及机制研究

项目名称： 单核细胞端粒酶活性在动脉粥样硬化中的作用及机制研究

项目编号： No.81500364

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： 王玉瑶

作者单位： 山西医科大学

项目金额： 18万元

中文摘要： 端粒及端粒酶在细胞衰老和炎症相关的动脉粥样硬化中发挥着重要作用。炎症因子的作用下，单核细胞向巨噬细胞的分化是动脉粥样硬化发生的关键环节。目前，外周血单核细胞端粒长度和端粒酶活性在动脉粥样硬化发生发展中的作用机制尚未完全阐明。我们基于前期工作，提出假设：端粒酶参与单核细胞向巨噬细胞分化过程并影响动脉粥样硬化的发生发展，其激活受NF-κB调控。本项目拟通过体外单核细胞培养、TERT表达干预小鼠、LDLr-/-动脉粥样硬化易感小鼠模型，采用基因过表达和siRNA基因敲低等技术研究炎症刺激下端粒酶活性的变化及其分子机制，进而在冠心病队列中评估外周血单核细胞端粒长度和端粒酶活性是否可作为心血管事件的预测指标。我们从细胞-动物-群体水平探讨单核细胞端粒和端粒酶活性在动脉粥样硬化进程中的作用及机制，将为动脉粥样硬化的防治提供新靶标。

中文关键词： 外周血单核细胞；端粒酶；端粒；动脉粥样硬化

英文摘要： Telomere regulation and telomerase activity play an important role in aging and the inflammatory remodeling during development of atherosclerosis. Accumulating data have shown that the differentiation of circulating monocytes into macrophages and their increased subendothelial infiltration are the pivotal steps during the atherosclerosis development. However, it remains unknown whether telomerase is activated in peripheral blood mononuclear cells in atherosclerosis. Therefore, we propose the hypothesis that telomerase is activated during the differentiation of monocytes into macrophages and the activation may be regulated by NF-κB. To investigate this hypothesis, we intend to study the regulatory role of telomerase in monocytes by overexpression of NF-κB and knockdown of hTERT with siRNA. Furthermore, we will investigate the telomere length and telomerase activity of peripheral blood mononuclear cells during atherosclerosis development in LDLr-/- mice and in patients with coronary heart disease. This study will provide new ideas for effective prevention of atherosclerosis.

英文关键词： Peripheral blood mononuclear cell;Telomerase;Telomere;Atherosclerosis