Corin介导的ANP活化在动脉粥样硬化形成及其炎症反应中的作用与机制

项目名称： Corin介导的ANP活化在动脉粥样硬化形成及其炎症反应中的作用与机制

项目编号： No.81200210

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： 姜晶晶

作者单位： 山东大学

项目金额： 23万元

中文摘要： Corin是ANP的活化酶。我们前期研究发现动脉粥样硬化病人血浆中Corin水平降低，提示Corin功能缺陷可能参与动脉粥样硬化病理过程。我们推测Corin通过介导ANP活化，进而影响血管壁的炎症反应，发挥抗动脉粥样硬化的作用。此外，我们在人脐静脉内皮细胞以及小鼠主动脉组织中检测到Corin的表达。结合先前关于ANP及其受体也在主动脉有表达的报道，我们提出主动脉壁存在一个局部的Corin-ANP系统, 参与血管壁的病理生理调节。本课题拟采用apoE基因敲除小鼠动脉粥样硬化模型，以及培养的动脉粥样硬化损伤细胞模型，体内外分别应用Corin或ANP基因敲除和基因沉默技术，深入探讨Corin在动脉粥样硬化及其炎症反应中的作用、机制以及与ANP活化的关系。同时通过在Corin基因敲除鼠的心脏再表达Corin cDNA，探讨心脏合成的Corin与血管壁局部合成的Corin各自发挥的作用。

中文关键词： Corin；动脉粥样硬化；心钠肽；ApoE-/-小鼠；

英文摘要： Corin is the long sought convertase of pro-ANP to active ANP. We found in our preliminary study that plasma Corin levels in patients with atherosclerotic disease became lower, suggesting the involvement of Corin deficiency in the pathological process of atherosclerosis. We hypothesize that Corin may inhibit the inflammatory response in the atherosclerotic lesion through its ANP activating function. In another experiment, we detected Corin expression in both cultured human umbilical vein endothelial cell (HUVEC) and mice aorta. Based on this discovery and earlier reports about the expression of ANP and its receptor in aorta tissue, we proposed that a local Corin-ANP system may exist in aorta wall, participating in the pathophysiological regulation of aorta. In the present study, we are going to take advantage of the apoE-deficiency atherosclerotic mice model and the in vitro cultured cell models for atherosclerotic lesion, to study the role of Corin in atherosclerosis initiation, its mechanism and the relevance to its ANP activation activity, by further knocking out Corin or ANP gene in vivo or silencing them in vitro, separately. At the same time, by introducing cardiac specifically expressed Corin cDNA back to Corin-/- mice, we will determine the effect of cardiac expressed Corin and Corin produced in aorta wal

英文关键词： Corin；atherosclerosis；ANP；ApoE-/- mice；