CyPA-EMMPRIN相互作用与动脉粥样硬化及斑块稳定性的关系研究

项目名称： CyPA-EMMPRIN相互作用与动脉粥样硬化及斑块稳定性的关系研究

项目编号： No.81200222

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： 袁伟

作者单位： 江苏大学

项目金额： 24万元

中文摘要： 研究提示亲环素A（CyPA）与细胞外基质金属蛋白酶诱导因子(EMMPRIN)均参与动脉粥样硬化（AS）形成，并与基质金属蛋白酶（MMPs）的产生有关。MMPs是削弱纤维帽诱发斑块破裂的重要细胞因子。我们前期研究发现CyPA水平与冠脉斑块不稳定相关，并且CyPA-EMMPRIN相互作用能促进单核细胞的炎症反应，诱导MMPs等炎症因子生成。因此，推测：CyPA与EMMPRIN二者在AS斑块发展进程中发挥重要作用；CyPA-EMMPRIN相互作用可能加速AS斑块的形成和不稳定性。本研究拟在前期研究基础上通过基因敲除鼠模型，从整体水平研究CyPA-EMMPRIN相互作用在调控AS斑块形成中作用；同时以单核细胞株为模型进行机制研究，分别过表达和沉默表达CyPA/EMMPRIN，验证CyPA-EMMPRIN相互作用对AS斑块形成影响，以期阐明CyPA-EMMPRIN相互作用调控斑块形成及下游事件发生。

中文关键词： 亲环素A；动脉粥样硬化；；；

英文摘要： It has been suggested that cyclophilin A (CyPA) and extracellular matrix metalloproteinase inducer (EMMPRIN) are involved in the formation of atherosclerosis (AS), with the expression of matrix metalloproteinases (MMPs). MMPs are important cytokines which can weaken the fibrous cap and induce the plaque rupture. Our previous study found that CyPA levels were closely related to the instability of coronary plaque. Moreover, the interaction of CyPA and EMMPRIN could stimulate monocytes to express some pro-inflammatory factors, including MMPs. Therefore, we presumed that both CyPA and EMMPRIN played important roles in the process of AS. CyPA-EMMPRIN interaction may accelerate the AS plaque formation and instability. Based on our preliminary studies, we will further demonstrate the roles of CyPA-EMMPRIN interaction in the regulation of AS plaque formation in this study. The gene knock-out mice model and cell model of monocyte will be used in the study. The over-expression or silence-expression of CyPA/EMMPRIN genes will be analyzed to verify the roles of CyPA-EMMPRIN interaction in AS plaque formation as well as in its downstream events.

英文关键词： cyclophilin A；atherosclerosis；；；