脂肪因子chemerin通过ChemR23依赖性途径对动脉粥样硬化发生、发展和斑块稳定性影响及其作用机制的研究

项目名称： 脂肪因子chemerin通过ChemR23依赖性途径对动脉粥样硬化发生、发展和斑块稳定性影响及其作用机制的研究

项目编号： No.81200212

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： 王旭平

作者单位： 山东大学

项目金额： 23万元

中文摘要： Chemerin是近年来发现的一种在先天性免疫和固有免疫中均发挥作用的脂肪因子，具有趋化免疫细胞向损伤部位聚集的作用。而且，这种趋化作用是具有受体依赖性的。我们在前期研究中发现，ChemR23作为chemerin的一种受体在血管内皮细胞、平滑肌细胞及巨噬细胞中均有表达；更有意思的是chemerin、chemR23在动脉粥样硬化(AS)斑块中也均表达，且在易损斑块中表达更高。我们拟通过构建ApoE-/-小鼠和ApoE-/-/ChemR23-/-双敲小鼠AS斑块形成及斑块不稳定模型，同时对其给予chemerin干预的方式，明确chemerin/ChemR23在AS及斑块稳定性中的作用；体外拟通过分别对培养的巨噬细胞、内皮和平滑肌细胞进行chemerin和ChemR23干预的方式，明确chemerin/ChemR23在上述细胞中的作用和信号通路，以期进一步明确二者在AS及斑块稳定性中的作用机制。

中文关键词： 脂肪因子；动脉粥样硬化；斑块稳定性；血管内皮细胞；血管平滑肌细胞

英文摘要： Chemerin was a recently identified novel adipokine that has a role in adaptive and innate immunity and is known to function as a chemoattractant that promotes recruitment of immune cells to sites of injury. Interestingly, the chemoattractant function of chemerin completely depends on chemerin R, and disappeared in ChemR23-/- mice. In previous studies, we found that ChemR23 were expressed in endothelial cells (ECs), smooth muscle cells (SMCs) and macrophages. Chemerin and ChemR23 were both demonstrated in atherosclerotic plaque in ApoE-/- mice. And a higher level was found in plaque with more prone to rupture, suggesting the potential role of chemerin and ChemR23 in the development of AS and in the instability of atherosclerotic plaque. Although accumulating studies suggest a plausible role of chemerin in metabolic disorders, its role in AS still remains unclear. We presume that the plausible mechanisms of the relationship between chemerin and AS could be as follows: 1) The high level of chemerin in atherosclerotic lesion could attract more immune cells through ChemR23 dependent signal pathway with contribute to the remodeling of the blood vessel wall, 2) The alteration of insulin sensitivity and glucose uptake in adipocytes and other vascular cells could contribute to development of AS, 3) Chemerin could direc

英文关键词： Adipokine；Atherosclerosis；Plaque Stability；Vascular Endothelial Cell；Vascular Smooth Muscle Cell