组蛋白甲基转移酶EZH2在慢性血栓栓塞性肺动脉高压血管重塑中的作用机制

项目名称： 组蛋白甲基转移酶EZH2在慢性血栓栓塞性肺动脉高压血管重塑中的作用机制

项目编号： No.81200042

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 王颖

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 血管重塑是慢性血栓栓塞性肺动脉高压（CTEPH)进展的重要因素。它主要涉及肺动脉内皮及平滑肌细胞的异常增殖，其间内皮间质细胞/平滑肌样细胞转化(EnMT)过程参与增殖平滑肌细胞组成，以上过程与肿瘤表现类似。组蛋白甲基转移酶EZH2在多种肿瘤中表达增高并通过表观遗传修饰发挥着重要的致癌作用。但EZH2在CTEPH血管重塑中的作用尚不明确。我们前期研究表明，EZH2在CTEPH病人肺血管平滑肌中出现明显的表达上调和胞浆表达。因此推测：EZH2在血管重塑的内皮和平滑肌细胞增殖及EnMT中可能发挥重要的作用。本项目将利用CTEPH组织和培养细胞为模型，研究1）EZH2在内皮和平滑肌细胞增殖和周期中的作用及机制2）EZH2在EnMT中起促进作用并明确其作用机制。3）EZH2用通过影响细胞骨架系统促进增殖平滑肌的运动。通过综合分析EZH2的作用机制，以期有效干预CTEPH的进展，找到更好的治疗方法。

中文关键词： 慢性血栓栓塞性肺动脉高压；血管重塑；肺动脉平滑肌；细胞迁移；甲基化

英文摘要： Pulmonary vascular remodeling in CTEPH mainly related to the abnormal proliferation of pulmonary artery endothelial and smooth muscle cells, during which the phenomenon of aendothelial cells be/ smooth muscle-like cells transition(EnMT) involved in the composition of proliferation of smooth muscle cells. The above procedure is similar to the tumor manifestations. The gene level of histone methyltransferase EZH2 increased was found in a variety of tumors and EZH2 play an important carcinogenic effects through epigenetic modifications. However, the role of EZH2 in CTEPH vascular remodeling are uncovered. Our previous studies showed that EZH2 was not only significantly upregulated but also expressed in cytoplasmic expression in pulmonary vascular smooth cells of CTEPH patients. We believe that: EZH2 may play important roles in the process of vascular endothelial and smooth muscle cell proliferation and EnMT in CTEPH. In this project we will use the CTEPH tissue and cultured cells as a model to study 1) The mechanism of EZH2in endothelial and smooth muscle cell proliferation and cell cycle.2) EZH2 lead to EnMT and the mechanism in this course.3)EZH2 promote the movement of PASMCs through effecting cell cytoskeleton. Through comprehensive analysis of the roles and mechanism of EZH2 in vascular remoding, we ai

英文关键词： Chronic thromboembolic pulmonary hypertension；vascular remodeling；pulmonary artery smooth muscle cells；cell migration；methylation